Research Article
BibTex RIS Cite

Network Pharmacology and Molecular Docking Perspectives into Lignans for Alzheimer's Disease Treatment

Year 2024, Volume: 27 Issue: Ek Sayı 1 (Suppl 1), 35 - 58

Seda Şirin , Serap Niğdelioğlu Dolanbay

https://doi.org/10.18016/ksutarimdoga.vi.1490753

Abstract

Alzheimer’s Disease (AD) is a debilitating neurodegenerative condition with limited treatment options. Lignans, a class of naturally occurring polyphenols found in various plants, have been shown to have the potential to modulate pathways associated with AD pathology. In this study, we used network pharmacology and molecular docking to investigate the therapeutic potential of lignans against AD by targeting specific proteins involved in disease progression. Our established interaction network includes key proteins such as EGFR, HSP90AA1, BCL2, HSP90AB1, IL6, JUN, ESR1, PIK3CA, ERBB2, and PIK3R1. Molecular docking studies have revealed how lignans interact with these proteins and highlighted their potential to influence AD through mechanisms such as inflammation modulation, apoptosis regulation, and signal transduction pathways. The results suggest that lignans have significant binding abilities to these targets, potentially inhibiting their activity and thus alleviating AD symptoms by reducing amyloid-beta accumulation and tau phosphorylation. These findings support the viability of lignans as a basis for the development of new AD therapies and call for further in vivo studies to confirm their efficacy and safety. This integrated approach underscores the value of combining network pharmacology and molecular docking in the search for new therapeutic agents against complex diseases such as AD.

Keywords

Alzheimer’s disease Lignan Molecular docking Network pharmacology

Project Number

-

References

  • Abadi, A.M., Zaki, M.S.A., Sideeg, A.M., El, A.F., & Guo, X. (2024). Determination of cytotoxicity, biological effects and anti-human breast cancer properties of Bilobol. Iranian Journal of Chemistry and Chemical Engineering (IJCCE), 1, 1-24.
  • Abd El-Razek, M.H., Eissa, I.H., Al-Karmalawy, A.A., Elrashedy, A.A., El-Desoky, A.H., Aboelmagd, M., Mohamed, T.A., Hegazy, M.E.F. (2024). epi-Magnolin, a tetrahydrofurofuranoid lignan from the oleo-gum resin of Commiphora wightii, as inhibitor of pancreatic cancer cell proliferation, in-vitro and in-silico study. Journal of Biomolecular Structure and Dynamics, 1, 1-13.
  • Abdul, H., Butterfield, D. (2007). Involvement of PI3K/PKG/ERK1/2 signaling pathways in cortical neurons to trigger protection by cotreatment of acetyl-L-carnitine and alpha-lipoic acid against HNE-mediated oxidative stress and neurotoxicity: Implications for Alzheimer's disease. Free Radical Biology & Medicine, 42(3), 371-84.
  • Aguilar-Carrillo, Y., Soto-Urzúa, L., Martínez-Martínez, M.D.L.Á., Becerril-Ramírez, M., Martínez-Morales, L.J. (2024). Computational analysis of the tripartite interaction of phasins (PhaP4 and 5)-sigma factor (σ24)-DNA of Azospirillum brasilense Sp7. Polymers, 16(5), 611.
  • Ahsan, A., Ramanand, S., Whitehead, C., Hiniker, S., Rehemtulla, A., Pratt, W., Jolly, S., Gouveia, C., Truong, K., Waes, C., Ray, D., Lawrence, T., Nyati, M. (2012). Wild-type EGFR is stabilized by direct interaction with HSP90 in cancer cells and tumors. Neoplasia, 14(8),670-677 .
  • Alam, M., Ali, S., Mohammad, T., Hasan, G.M., Yadav, D.K., Hassan, M.I. (2021). B cell lymphoma 2: a potential therapeutic target for cancer therapy. International Journal of Molecular Sciences, 22(19), 10442.
  • Arjmandi-Rad, S., Vestergaard Nieland, J.D., Goozee, K.G., Vaseghi, S. (2024). The effects of different acetylcholinesterase inhibitors on EEG patterns in patients with Alzheimer’s disease: A systematic review. Neurological Sciences, 45(2), 417-430.
  • Astillero‐Lopez, V., Villar‐Conde, S., Gonzalez‐Rodriguez, M., Flores‐Cuadrado, A., Ubeda‐Banon, I., Saiz‐Sanchez, D., Martinez‐Marcos, A. (2024). Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aβ pathology through microglial and astroglial cells. Brain Pathology, e13235.
  • Atoki, A.V., Aja, P.M., Shinkafi, T.S., Ondari, E.N., Awuchi, C.G. (2023). Naringenin: its chemistry and roles in neuroprotection. Nutritional Neuroscience, 1, 1-30.
  • Austin, S., Katusic, Z. (2016). Loss of endothelial nitric oxide synthase promotes p25 generation and tau phosphorylation in a murine model of Alzheimer's disease. Circulation Research, 119(10), 1128-1134.
  • Behl, C., Hovey, L., Krajewski, S., Schubert, D., Reed, J. (1993). BCL-2 prevents killing of neuronal cells by glutamate but not by amyloid beta protein. Biochemical and Biophysical Research Communications, 197(2), 949-56.
  • Bindea, G., Mlecnik, B., Hackl, H., Charoentong, P., Tosolini, M., Kirilovsky, A., Fridman, W.H., Pages, F., Trajanoski, Z., Galon, J. (2009). ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics, 25(8), 1091-1093.
  • Birkinshaw, R. W., Gong, J. N., Luo, C. S., Lio, D., White, C. A., Anderson, M. A., Blombery, P., Lessene, G., Majewski, I. J., Thijssen, R., Roberts, A. W., Huang, D. C. S., Colman, P. M., & Czabotar, P. E. (2019). Structures of BCL-2 in complex with venetoclax reveal the molecular basis of resistance mutations. Nature Communications, 10(1), 2385.
  • Boada, M., Antunez, C., López-arrieta, J., Caruz, A., Moreno-Rey, C., Ramírez-Lorca, R., Morón, F., Hernández, I., Mauleon, A., Rosende-Roca, M., Martínez-Lage, P., Marín, J., Tárraga, L., Alegret, M., Pedrajas, J., Urda, N., Royo, J., Sáez, M., Gayán, J., Gonzáléz-Pérez, A., Real, L., Ruiz, A., Galán, J. (2012). Estrogen receptor alpha gene variants are associated with Alzheimer's disease. Neurobiology of Aging, 33, 198.e15-198.e24.
  • Bohush, A., Bieganowski, P., Filipek, A. (2019). Hsp90 and its co-chaperones in neurodegenerative diseases. International Journal of Molecular Sciences, 20(20), 4976.
  • Borsari, C., Keles, E., McPhail, J. A., Schaefer, A., Sriramaratnam, R., Goch, W., Schaefer, T., De Pascale, M., Bal, W., Gstaiger, M., Burke, J. E., & Wymann, M. P. (2022). Covalent Proximity Scanning of a Distal Cysteine to Target PI3Kα. Journal of the American Chemical Society, 144(14), 6326–6342.
  • Bredt, D., Ferris, C., Snyder, S. (1992). Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification of flavin and calmodulin binding sites. The Journal of Biological Chemistry, 267(16), 10976-81.
  • Casara, P., Davidson, J., Claperon, A., Le Toumelin-Braizat, G., Vogler, M., Bruno, A., Chanrion, M., Lysiak-Auvity, G., Le Diguarher, T., Starck, J. B., Chen, I., Whitehead, N., Graham, C., Matassova, N., Dokurno, P., Pedder, C., Wang, Y., Qiu, S., Girard, A. M., Schneider, E.,Grave, F., Studeny, A., Guasconi, G., Rocchetti, F., Maiga, S., Henlin, J.M., Colland, F., Kraus-Berthier, L., Le Gouill, S., Dyer, M.J.S., Hubbard, R., Wood, M., Amioti M., Cohen, G.M., Hickman, J.A., Morris, E., Murray, J., Geneste, O. (2018). S55746 is a novel orally active BCL-2 selective and potent inhibitor that impairs hematological tumor growth. Oncotarget, 9(28), 20075–20088.
  • Cedillo-Cortezano, M., Martinez-Cuevas, L.R., López, J.A.M., Barrera López, I.L., Escutia-Perez, S., Petricevich, V. L. (2024). Use of medicinal plants in the process of wound healing: A literature review. Pharmaceuticals, 17(3), 303.
  • Chen, L., Zhang, Y., Wang, S., Zhang, Y., Huang, T., Cai, Y. (2017). Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways. PLoS ONE, 12.
  • Chopade, A.R., Pol, R.P., Patil, P.A., Dharanguttikar, V.R., Naikwade, N.S., Dias, R.J., Mali, S.N. (2021). An insight into the anxiolytic effects of lignans (phyllanthin and hypophyllanthin) and tannin (corilagin) rich extracts of Phyllanthus amarus: An &in-silico and in-vivo approaches. Combinatorial Chemistry & High Throughput Screening, 24(3), 415-422.
  • Daina, A., Michielin, O., Zoete, V. (2014). iLOGP: a simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. Journal of Chemical Information and Modeling, 54(12), 3284-3301.
  • Daina, A., Michielin, O. (2016). A BOILED-Egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem, 11(11), 1117-1121.
  • Daina, A., Michielin, O., Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7, 42717.
  • Dent, P., Booth, L., Roberts, J., Poklepovic, A., Cridebring, D., Reiman, E. (2021). Inhibition of heat shock proteins increases autophagosome formation, and reduces the expression of APP, Tau, SOD1 G93A and TDP-43. Aging, 13, 17097 - 17117.
  • Dissanayaka, D.S., Jayasena, V., Rainey-Smith, S.R., Martins, R.N., Fernando, W.B. (2024). The role of diet and gut microbiota in Alzheimer’s disease. Nutrients, 16(3), 412.
  • Eccles, S.A. (2011). The epidermal growth factor receptor/Erb-B/HER family in normal and malignant breast biology. The International Journal of Developmental Biology, 55(7-9), 685-96.
  • Eckert, A., Keil, U., Marques, C.A., Bonert, A., Frey, C., Schüssel, K., Müller, W.E. (2003). Mitochondrial dysfunction, apoptotic cell death, and Alzheimer’s disease. Biochemical Pharmacology, 66(8), 1627-1634.
  • Fakhri, S., Iranpanah, A., Gravandi, M. M., Moradi, S. Z., Ranjbari, M., Majnooni, M. B., Echeverria, J., Qi, Y., Wang, M., Liao, P., Farzaei, M.H., Xiao, J. (2021). Natural products attenuate PI3K/Akt/mTOR signaling pathway: A promising strategy in regulating neurodegeneration. Phytomedicine, 91, 153664.
  • Franceschini, A., Lin, J., von Mering, C., Jensen, L.J. (2016). SVD-phy: improved prediction of protein functional associations through singular value decomposition of phylogenetic profiles. Bioinformatics, 32(7), 1085-1087.
  • Franceschini, A., Szklarczyk, D., Frankild, S., Kuhn, M., Simonovic, M., Roth, A., Lin, J., Minguez, P., Bork, P., von Mering, C., Jensen, L.J. (2012). STRING v9. 1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Research, 41(D1), D808-D815.
  • Fraser, M., Bayazitov, I., Zakharenko, S., Baker, S. (2008). Phosphatase and tensin homolog, deleted on chromosome 10 deficiency in brain causes defects in synaptic structure, transmission and plasticity, and myelination abnormalities. Neuroscience, 151, 476-488.
  • Ge, S.X., Jung, D., Yao, R. (2020). ShinyGO: a graphical gene-set enrichment tool for animals and plants Bioinformatics, 36, 2628–2629.
  • Gene Ontology Consortium (2017). Expansion of the Gene Ontology knowledgebase and resources. Nucleic Acids Research, 45, D331 - D338.
  • Gobom, J., Brinkmalm, A., Brinkmalm, G., Blennow, K., Zetterberg, H. (2024). Alzheimer's disease biomarker analysis using targeted mass spectrometry. Molecular & Cellular Proteomics, 23(2),100721.
  • Gong, C., Iqbal, K. (2008). Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Current Medicinal Chemistry, 15(23), 2321-2328.
  • Gonzalez-Rodriguez, M., Villar-Conde, S., Astillero-Lopez, V., Villanueva-Anguita, P., Ubeda-Banon, I., Flores-Cuadrado, A., Martinez-Marcos, A., Saiz-Sanchez, D. (2021). Neurodegeneration and Astrogliosis in the Human CA1 Hippocampal Subfield Are Related to hsp90ab1 and bag3 in Alzheimer’s Disease. International Journal of Molecular Sciences, 23(1), 165.
  • Hernández, P., Lee, G., Sjoberg, M., Maccioni, R.B. (2009). Tau phosphorylation by cdk5 and Fyn in response to amyloid peptide Aβ (25-35): involvement of lipid rafts. Journal of Alzheimer's Disease, 16(1), 149-156.
  • Hoang, S.H., Lam, E.M., Dao, H. (2024). Computational assessment of gut microbiota metabolite enterolactone as a promising Aβ42 inhibitor in Alzheimer's disease. DYSONA-Life Science, 5(1), 9-20.
  • Hopkins, A.L. (2007). Network pharmacology: The next paradigm in drug discovery. Nature Chemical Biology, 3(11), 682-690.
  • Hoxhaj, G., Manning, B.D. (2020). The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism. Nature Reviews Cancer, 20(2), 74-88.
  • Hoter, A., El-Sabban, M.E., Naim, H.Y. (2018). The HSP90 family: structure, regulation, function, and implications in health and disease. International Jurnal of Molecular Sciences, 19(9), 2560.
  • Huang, D.W., Sherman, B.T., Lempicki, R.A. (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols, 4(1), 44-57.
  • Ibrahim, M., Uzairu, A., Shallangwa, G., & Uba, S. (2020). In-silico activity prediction and docking studies of some 2, 9-disubstituted 8-phenylthio/phenylsulfinyl-9h-purine derivatives as Anti-proliferative agents. Heliyon, 6(1), e03158.
  • Ibrahim, M.T., Uzairu, A., Uba, S., Shallangwa, G.A. (2020). Computational modeling of novel quinazoline derivatives as potent epidermal growth factor receptor inhibitors. Heliyon, 6(2), e03289.
  • Jayaswamy, P.K., Vijaykrishnaraj, M., Patil, P., Alexander, L.M., Kellarai, A., Shetty, P. (2023). Implicative role of epidermal growth factor receptor and its associated signaling partners in the pathogenesis of Alzheimer’s disease. Ageing Research Reviews, 83, 101791.
  • Jensen, L.J., Kuhn, M., Stark, M., Chaffron, S., Creevey, C., Muller, J., Doerks, T., Julien, P., Roth, A., Simonovic, M., Bork, P., von Mering, C. (2009). STRING 8—a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Research, 37(suppl_1), D412-D416.
  • Jimenez, S., Torres, M., Vizuete, M., Sanchez-Varo, R., Sanchez-Mejias, E., Trujillo-Estrada, L., Carmona-Cuenca, I., Caballero, C., Ruano, Gutierrez, A., Vitorica, J. (2011). Age-dependent accumulation of soluble amyloid β (Aβ) oligomers reverses the neuroprotective effect of soluble amyloid precursor protein-α (sAPPα) by modulating phosphatidylinositol 3-kinase (PI3K)/Akt-GSK-3β pathway in Alzheimer mouse model. Journal of Biological Chemistry, 286(21), 18414-18425.
  • Kumar, M., Bansal, N. (2022). Implications of phosphoinositide 3-kinase-Akt (PI3K-Akt) pathway in the pathogenesis of Alzheimer’s disease. Molecular Neurobiology, 59(1), 354-385.
  • Kummer, K.K., Zeidler, M., Kalpachidou, T., Kress, M. (2021). Role of IL-6 in the regulation of neuronal development, survival and function. Cytokine, 144, 155582.
  • Lan, Y.L., Zhao, J., Li, S. (2015). Update on the neuroprotective effect of estrogen receptor alpha against Alzheimer's disease. Journal of Alzheimer's Disease, 43(4), 1137-1148.
  • Ledonne, A., Mango, D., Latagliata, E.C., Chiacchierini, G., Nobili, A., Nisticò, R., D’Amelio, M., Puglisi-Allegra, S., Mercuri, N.B. (2018). Neuregulin 1/ErbB signalling modulates hippocampal mGluRI-dependent LTD and object recognition memory. Pharmacological Research, 130, 12-24.
  • Lee, K.H., Lee, S.J., Lee, H.J., Choi, G., Jung, Y., Kim, D.I., Gabr, A., Ryu, J.M., Han, H. (2017). Amyloid β1-42 (Aβ1-42) induces the CDK2-mediated phosphorylation of tau through the activation of the mTORC1 signaling pathway while promoting neuronal cell death. Frontiers in Molecular Neuroscience, 10.
  • Lei, S., Wu, S., Wang, G., Li, B., Liu, B., Lei, X. (2021). Pinoresinol diglucoside attenuates neuroinflammation, apoptosis and oxidative stress in a mice model with Alzheimer’s disease. Neuroreport, 32(3), 259-267.
  • Li, B., Ma, W., Jaffe, H., Zheng, Y., Takahashi, S., Zhang, L., Kulkarni, A., Pant, H. (2003). Cyclin-dependent kinase-5 is involved in neuregulin-dependent activation of phosphatidylinositol 3-kinase and Akt activity mediating neuronal survival. Journal of Biological Chemistry, 278, 35702-35709.
  • Li, S., Zhang, B., Zhang, N., Zhang, Y. (2011). Network pharmacology: a new approach for chinese herbal medicine research. Evidence-Based Complementary and Alternative Medicine, 2011.
  • Liebermann, D.A., Gregory, B., Hoffman, B. (1998). AP-1 (Fos/Jun) transcription factors in hematopoietic differentiation and apoptosis. International Journal of Oncology, 12(3), 685-1385.
  • Liu, J., Yuan, S., Niu, X., Kelleher, R., Sheridan, H. (2022b). ESR1 dysfunction triggers neuroinflammation as a critical upstream causative factor of the Alzheimer’s disease process. Aging, 14, 8595-8614.
  • Liu, Y., Yang, X., Gan, J., Chen, S., Xiao, Z.X., Cao, Y. (2022a). CB-Dock2: Improved protein–ligand blind docking by integrating cavity detection, docking and homologous template fitting. Nucleic Acids Research, 50(W1), W159-W164.
  • Lu, C., Fu, W., Zhao, D., Mattson, M. P. (2002). The DNA damaging agent etoposide activates a cell survival pathway involving α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptors and mitogen‐activated protein kinases in hippocampal neurons. Journal of Neuroscience Research, 70(5), 671-679.
  • Lyra e Silva, N.M., Gonçalves, R.A., Pascoal, T.A., Lima-Filho, R.A., Resende, E.D.P.F., Vieira, E.L., Texeira, A.L., de Souza, L.C., Peny, J.A., Fortuna, J.T.S., Furigo, I.C., Hashiguchi, D., Miya-Coreixas, V.S., Clarke, J.R., Abisambrai J.F., Longo, B.M., Donato Jr, J., Eraser, P.E., Rosa-Neto, P., Caramelli, P., Ferreira, S.T., De Felice, F.G. (2021). Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer’s disease. Translational Psychiatry, 11(1), 251.
  • Maiese, K., Chong, Z.Z. (2004). Insights into oxidative stress and potential novel therapeutic targets for Alzheimer disease. Restorative Neurology and Neuroscience, 22(2), 87-104.
  • Majahan, A., Sharma, N., Ulhe, A., Patil, R., Hegde, M., Mali, A. (2024). From dietary lignans to cancer therapy: Integrative systems analysis of enterolactone's molecular targets and signaling pathways in combatting cancer stem cells in triple-negative breast cancer. Food Bioscience, 58(5-6), 103732.
  • Martini, M., De Santis, M.C., Braccini, L., Gulluni, F., Hirsch, E. (2014). PI3K/AKT signaling pathway and cancer: an updated review. Annals of Medicine, 46(6), 372-383.
  • Maximov, P. Y., Abderrahman, B., Fanning, S. W., Sengupta, S., Fan, P., Curpan, R. F., Rincon, D. M. Q., Greenland, J. A., Rajan, S. S., Greene, G. L., & Jordan, V. C. (2018). Endoxifen, 4-Hydroxytamoxifen and an estrogenic derivative modulate estrogen receptor complex mediated apoptosis in breast cancer. Molecular Pharmacology, 94(2), 812–822.
  • Miller, M. S., Maheshwari, S., McRobb, F. M., Kinzler, K. W., Amzel, L. M., Vogelstein, B., & Gabelli, S. B. (2017). Identification of allosteric binding sites for PI3Kα oncogenic mutant specific inhibitor design. Bioorganic & medicinal chemistry, 25(4), 1481–1486.
  • Miron, J., Picard, C., Frappier, J., Dea, D., Théroux, L., Poirier, J. (2018). TLR4 gene expression and pro-inflammatory cytokines in Alzheimer's sisease and in response to hippocampal deafferentation in rodents. Journal of Alzheimer's disease: JAD, 63(4), 1547-1556.
  • Mishra, S., Dahima, R. (2019). In vitro ADME studies of TUG-891, a GPR-120 inhibitor using SWISS ADME predictor. Journal of Drug Delivery and Therapeutics, 9(2-s), 366-369.
  • Mohammadi, M.K., Firuzi, O., Khoshneviszadeh, M., Razzaghi-Asl, N., Sepehri, S., & Miri, R. (2014). Novel 9-(alkylthio)-Acenaphtho[1,2-e]-1,2,4-triazine derivatives: synthesis, cytotoxic activity and molecular docking studies on B-cell lymphoma 2 (Bcl-2). DARU Journal of Pharmaceutical Sciences, 22, 1-11.
  • Muchtaridi, M., Syahidah, H. N., Subarnas, A., Yusuf, M., Bryant, S. D., & Langer, T. (2017). Molecular docking and 3D-pharmacophore modeling to study the interactions of chalcone derivatives with estrogen receptor alpha. Pharmaceuticals, 10(4), 81.
  • Munkley, J., Livermore, K. E., McClurg, U. L., Kalna, G., Knight, B., McCullagh, P., McGrath, J., Crundwell, M., Leung, H.Y., Robson, C.N., Harries, L.W., Rajan, P., Elliott, D. J. (2015). The PI3K regulatory subunit gene PIK3R1 is under direct control of androgens and repressed in prostate cancer cells. Oncoscience, 2(9), 755.
  • Murray, J. B., Davidson, J., Chen, I., Davis, B., Dokurno, P., Graham, C. J., Harris, R., Jordan, A., Matassova, N., Pedder, C., Ray, S., Roughley, S. D., Smith, J., Walmsley, C., Wang, Y., Whitehead, N., Williamson, D. S., Casara, P., Le Diguarher, T., Hickman, J., Stark, J., Kotschy, A., Geneste, O., Hubbard, R. E. (2019). Establishing Drug Discovery and Identification of Hit Series for the Anti-apoptotic Proteins, Bcl-2 and Mcl-1. ACS Omega, 4(5), 8892–8906.
  • Nag, A., Verma, P., Paul, S., Kundu, R. (2022). In silico analysis of the apoptotic and HPV inhibitory roles of some selected phytochemicals detected from the rhizomes of greater cardamom. Applied Biochemistry and Biotechnology, 194(10), 4867-4891.
  • Nawfetrias, W., Devy, L., Esyanti, R.R., Faizal, A. (2024). Phyllanthus lignans: A review of biological activity and elicitation. Horticulturae, 10(2), 195.
  • Oliveira, J., Costa, M., Almeida, M., Silva, O., Henriques, A. (2017). Protein phosphorylation is a key mechanism in Alzheimer's disease. Journal of Alzheimer's disease: JAD, 58(4), 953-978.
  • Oliveira Silva, R., Counil, H., Rabanel, J.M., Haddad, M., Zaouter, C., Ben Khedher, M. R., Patten, S.A., Ramassamy, C. (2024). Donepezil-loaded nanocarriers for the treatment of Alzheimer’s disease: Superior efficacy of extracellular vesicles over polymeric nanoparticles. International Journal of Nanomedicine, 1077-1096.
  • Ou, G.Y., Lin, W.W., Zhao, W.J. (2021). Neuregulins in neurodegenerative diseases. Frontiers in Aging Neuroscience, 13, 662474.
  • Parihar, M.S., Brewer, G.J. (2010). Amyloid-β as a modulator of synaptic plasticity. Journal of Alzheimer's Disease, 22(3), 741-763.
  • Park, J. H., Liu, Y., Lemmon, M. A., & Radhakrishnan, R. (2012). Erlotinib binds both inactive and active conformations of the EGFR tyrosine kinase domain. Biochemical Journal, 448(Pt 3), 417.
  • Park, K.W. (2024). Anti-amyloid Antibody Therapies for Alzheimer’s Disease. Nuclear Medicine and Molecular Imaging, 1-10.
  • Pattar, S. V., Adhoni, S. A., Kamanavalli, C. M., & Kumbar, S. S. (2020). In silico molecular docking studies and MM/GBSA analysis of coumarin-carbonodithioate hybrid derivatives divulge the anticancer potential against breast cancer. Beni-Suef University Journal of Basic and Applied Sciences, 9, 1-10.
  • Paul, D., Mahanta, S., Tag, H., Das, S.K., Das Gupta, D., Tanti, B., Ananthan, R., Das, R., Jambhulkar, S. & Hui, P.K. (2021). Identification of tyrosine kinase inhibitors from Panax bipinnatifidus and Panax pseudoginseng for RTK—HER2 and VEGFR2 receptors, by in silico approach. Molecular Diversity, 1-23.
  • Pike, C.J. (2017). Sex and the development of Alzheimer's disease. Journal of Neuroscience Research, 95(1-2), 671-680.
  • Prete, D., Rice, R., Rajadhyaksha, A., D’Adamio, L. (2016). Amyloid precursor protein (APP) may act as a substrate and a recognition unit for CRL4CRBN and Stub1 E3 ligases facilitating ubiquitination of proteins involved in presynaptic functions and neurodegeneration. The Journal of Biological Chemistry, 291, 17209-17227.
  • Qin, Y., Yang, P., He, W., Li, D., Zeng, L., Li, J., Zhou, T., Peng, J., Cao, L., Huang, W. (2024). Novel histone post-translational modifications in Alzheimer’s disease: current advances and implications. Clinical Epigenetics, 16(1), 39.
  • Qu, W.S., Liu, J.L., Li, C.Y., Li, X., Xie, M.J., Wang, W., Tian, D.S. (2015). Rapidly activated epidermal growth factor receptor mediates lipopolysaccharide-triggered migration of microglia. Neurochemistry international, 90, 85-92.
  • Quiroga, R., Villarreal, M.A. (2016). Vinardo: A scoring function based on autodock vina improves scoring, docking, and virtual screening. PloS One, 11(5), e0155183.
  • Rajmohan, R., Reddy, P.H. (2017). Amyloid-beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer’s disease neurons. Journal of Alzheimer's Disease, 57(4), 975-999.
  • Razani, E., Pourbagheri-Sigaroodi, A., Safaroghli-Azar, A., Zoghi, A., Shanaki-Bavarsad, M., Bashash, D. (2021). The PI3K/Akt signaling axis in Alzheimer’s disease: a valuable target to stimulate or suppress?. Cell Stress and Chaperones, 26(6), 871-887.
  • Reddy, V. P., Aryal, P., Robinson, S., Rafiu, R., Obrenovich, M., Perry, G. (2020). Polyphenols in Alzheimer’s disease and in the gut–brain axis. Microorganisms, 8(2), 199.
  • Roe, S. M., Prodromou, C., O'Brien, R., Ladbury, J. E., Piper, P. W., & Pearl, L. H. (1999). Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. Journal of Medicinal Chemistry, 42(2), 260–266.
  • Rubio-Perez, J.M., Morillas-Ruiz, J.M. (2012). A review: Inflammatory process in Alzheimer's disease, role of cytokines. The Scientific World Journal, 2012(1), 756357.
  • Russell, J.K., Jones, C.K., Newhouse, P.A. (2019). The role of estrogen in brain and cognitive aging. Neurotherapeutics, 16(3), 649-665.
  • Salminen, A., Kauppinen, A., Suuronen, T., Kaarniranta, K., Ojala, J. (2009). ER stress in Alzheimer's disease: a novel neuronal trigger for inflammation and Alzheimer's pathology. Journal of Neuroinflammation, 6, 1-13.
  • Sato, K., Takayama, K.I., Inoue, S. (2023). Expression and function of estrogen receptors and estrogen-related receptors in the brain and their association with Alzheimer’s disease. Frontiers in Endocrinology, 14, 1220150.
  • Scorrano, L., Korsmeyer, S.J. (2003). Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochemical and Biophysical Research Communications, 304(3), 437-444.
  • Shacka, J.J., Roth, K.A. (2005). Regulation of neuronal cell death and neurodegeneration by members of the Bcl-2 family: therapeutic implications. Current Drug Targets-CNS & Neurological Disorders, 4(1), 25-39.
  • Sharma, S., & Kumar, P. (2023). Deciphering the molecular mechanism of HSP90AB1 as a potential heat shock protein and understanding the role of alkaloids in the therapeutic suppression of glioblastomas (GBMs). In 2023 3rd International Conference on Innovative Sustainable Computational Technologies (CISCT) (pp. 1-5). IEEE.
  • Shaw, S., Bourne, T., Meier, C., Carrington, B., Gelinas, R., Henry, A., Popplewell, A., Adams, R., Baker, T., Rapecki, S., Marshall, D., Moore, A., Neale, H., & Lawson, A. (2014). Discovery and characterization of olokizumab: a humanized antibody targeting interleukin-6 and neutralizing gp130-signaling. mAbs, 6(3), 774–782.
  • Shtaiwi, A., Adnan, R., Khairuddean, M., & Khan, S. U. (2019). Computational investigations of the binding mechanism of novel benzophenone imine inhibitors for the treatment of breast cancer. RSC Advances, 9(61), 35401-35416.
  • Snel, B., Lehmann, G., Bork, P., & Huynen, M. A. (2000). STRING: a web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. Nucleic Acids Research, 28(18), 3442-3444.
  • Sontag, J., Sontag, E. (2014). Protein phosphatase 2A dysfunction in Alzheimer’s disease. Frontiers in Molecular Neuroscience, 7, 16.
  • Souza, D.C.S., Costa‐Silva, T.A., Morais, T.R., Brito, J.R., Ferreira, E.A., Antar, G.M., Sartorelli, P., Tempone, A.G., Lago, J.H.G. (2021). Simplified derivatives of dibenzylbutyrolactone lignans from Hydrocotyle bonariensis as antitrypanosomal candidates. Chemistry & Biodiversity, 18(10), e2100515.
  • Stebbins, C. E., Russo, A. A., Schneider, C., Rosen, N., Hartl, F. U., & Pavletich, N. P. (1997). Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell, 89(2), 239–250.
  • Sundermann, E.E., Maki, P.M., Bishop, J.R. (2010). A review of estrogen receptor α gene (ESR1) polymorphisms, mood, and cognition. Menopause, 17(4), 874-886.
  • Szklarczyk, D., Franceschini, A., Kuhn, M., Simonovic, M., Roth, A., Minguez, P., Doerks, T., Stark, M., Muller, J., Bork, P., Jensen, L.J., Mering, C.V. (2010). The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Research, 39(suppl_1), D561-D568.
  • Szklarczyk, D., Franceschini, A., Wyder, S., Forslund, K., Heller, D., Huerta-Cepas, J., Simonovic, M., Roth, A., Santos, A., Tsafou, K.P., Kuhn, M., Bork, P., Jensen, L.J., Von Mering, C. (2015). STRING v10: protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Research, 43(D1), D447-D452.
  • Szklarczyk, D., Gable, A. L., Lyon, D., Junge, A., Wyder, S., Huerta-Cepas, J., Simonovic, M., Doncheva, N.T., Morris, J.H., Bork, P., Jensen, L.J. Mering, C.V. (2019). STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Research, 47(D1), D607-D613.
  • Szklarczyk, D., Kirsch, R., Koutrouli, M., Nastou, K., Mehryary, F., Hachilif, R., Annika, G.L., Fang, T., Doncheva, N.T., Pyysalo, S., Bork, P., Jensen, L.J., von Mering, C. (2023). The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Research, 51(D1), D638-D646.
  • Szklarczyk, D., Morris, J.H., Cook, H., Kuhn, M., Wyder, S., Simonovic, M., Santos, A., Doncheva, N.T., Roth, A., Bork, P., Jensen, L.J., Von Mering, C. (2016). The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Research, 45, D362-68.
  • Tavassoly, O., Sato, T., Tavassoly, I. (2020). Inhibition of brain epidermal growth factor receptor activation: a novel target in neurodegenerative diseases and brain injuries. Molecular Pharmacology, 98(1), 13-22.
  • Thangavel, N., Al Bratty, M., Al Hazmi, H.A., Najmi, A., Ali Alaqi, R.O. (2021). Molecular docking and molecular dynamics aided virtual search of OliveNet™ Directory for Secoiridoids to combat SARS-CoV-2 infection and associated hyperinflammatory responses. Frontiers in Molecular Biosciences, 7, 627767.
  • Ugurlu, S.Y., McDonald, D., Lei, H., Jones, A.M., Li, S., Tong, H.Y., Butler, M.S., He, S. (2024). Cobdock: an accurate and practical machine learning-based consensus blind docking method. Journal of Cheminformatics, 16(1), 5.
  • URL1 https://cadd.labshare.cn/cb-dock2/index.php
  • URL2 https://www.rcsb.org/structure/3UG2
  • URL3 https://www.rcsb.org/structure/4HJO
  • URL4 https://www.rcsb.org/structure/1XKK
  • URL5 https://www.rcsb.org/structure/1yet
  • URL6 https://www.rcsb.org/structure/1yes
  • URL7 https://www.rcsb.org/structure/1BGQ
  • URL8 https://www.rcsb.org/structure/6qgg
  • URL9 https://www.rcsb.org/structure/6O0K
  • URL10 https://www.rcsb.org/structure/6GL8
  • URL11 https://www.rcsb.org/structure/4CNI
  • URL12 https://www.rcsb.org/structure/5w9c
  • URL13 https://www.rcsb.org/structure/7R9V
  • URL14 https://www.rcsb.org/structure/5SX8
  • URL15 https://www.intechopen.com/chapters/75508
  • URL16 http://zhanggroup.org/BioLiP2/pdb/single/ 1E7U
  • URL17 http://zhanggroup.org/BioLiP2/pdb/single/ 1E7V
  • URL18 http://zhanggroup.org/BioLiP2/pdb/single/ 1E7W
  • Von Mering, C., Huynen, M., Jaeggi, D., Schmidt, S., Bork, P., Snel, B. (2003). STRING: a database of predicted functional associations between proteins. Nucleic Acids Research, 31(1), 258-261.
  • Von Mering, C., Jensen, L. J., Kuhn, M., Chaffron, S., Doerks, T., Krüger, B., Snel, B., Bork, P. (2007). STRING 7—recent developments in the integration and prediction of protein interactions. Nucleic Acids Research, 35(suppl_1), D358-D362.
  • Von Mering, C., Jensen, L. J., Snel, B., Hooper, S. D., Krupp, M., Foglierini, M., Jouffre, N., Huynen, M.A., Bork, P. (2005). STRING: known and predicted protein–protein associations, integrated and transferred across organisms. Nucleic Acids Research, 33(suppl_1), D433-D437.
  • Wang, B.J., Her, G.M., Hu, M.K., Chen, Y.W., Tung, Y.T., Wu, P.Y., Hsu, W.M., Lee, H., Jin, L.W., Hwang, S.P.L., Chen, R.P.Y., Huang, C.J., Liao, Y.F. (2017). ErbB2 regulates autophagic flux to modulate the proteostasis of APP-CTFs in Alzheimer’s disease. Proceedings of the National Academy of Sciences, 114(15), E3129-E3138.
  • Webers, A., Heneka, M.T., Gleeson, P.A. (2020). The role of innate immune responses and neuroinflammation in amyloid accumulation and progression of Alzheimer's disease. Immunology and Cell Biology, 98(1), 28-41.
  • Weinkove, D., Bastiani, M., Chessa, T., Joshi, D., Hauth, L., Cooke, F., Divecha, N., Schuske, K. (2008). Overexpression of PPK-1, the Caenorhabditis elegans Type I PIP kinase, inhibits growth cone collapse in the developing nervous system and causes axonal degeneration in adults. Developmental Biology, 313(1), 384-97 .
  • Weisman, D., Hakimian, E., Ho, G.J. (2006). Interleukins, inflammation, and mechanisms of Alzheimer's disease. Vitamins & Hormones, 74, 505-530.
  • Wood, E. R., Truesdale, A. T., McDonald, O. B., Yuan, D., Hassell, A., Dickerson, S. H., Ellis, B., Pennisi, C., Horne, E., Lackey, K., Alligood, K.J., Rusnak, D.W., Gilmer, T.M. & Shewchuk, L. (2004). A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib) relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Research, 64(18), 6652-6659.
  • Wu, L., Xiong, X., Wu, X., Ye, Y., Jian, Z., Zhi, Z., Gu, L. (2020). Targeting oxidative stress and inflammation to prevent ischemia-reperfusion injury. Frontiers in Molecular Neuroscience, 13, 28.
  • Xie, C., Mao, X., Huang, J., Ding, Y., Wu, J., Dong, S., Kong, L., Gao, G., Li, C.Y., Wei, L. (2011). KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases. Nucleic Acids Research, 39(suppl_2), W316-W322.
  • Xing, Z., Chu, C., Chen, L., Kong, X. (2016). The use of Gene Ontology terms and KEGG pathways for analysis and prediction of oncogenes. Biochimica et Biophysica Acta, 1860(11),2725-34.
  • Xu, S., Li, X., Liu, S., Tian, P., Li, D. (2022). Juniperus sabina L. as a source of Podophyllotoxins: Extraction optimization and anticholinesterase activities. International Journal of Molecular Sciences, 23(18), 10205.
  • Yang, X., Liu, Y., Gan, J., Xiao, Z.X., Cao, Y. (2022). FitDock: Protein–ligand docking by template fitting. Briefings in Bioinformatics, 23(3), bbac087.
  • Yarza, R., Vela, S., Solas, M., Ramirez, M.J. (2016). c-Jun N-terminal kinase (JNK) signaling as a therapeutic target for Alzheimer’s disease. Frontiers in Pharmacology, 6, 321.
  • Yoshikawa, S., Kukimoto-Niino, M., Parker, L., Handa, N., Terada, T., Fujimoto, T., Terazawa, Y., Wakiyama, M., Sato, M., Sano, S., Kobayashi, T., Tanaka, T., Chen, L., Liu, Z-J., Wang, B-C., Shirouzu, M., Kawa, S., Semba, K., Yamamoto, T., & Yokoyama, S. (2013). Structural basis for the altered drug sensitivities of non-small cell lung cancer-associated mutants of human epidermal growth factor receptor. Oncogene, 32(1), 27-38.
  • Zeng, J., Weng, Y., Lai, T., Chen, L., Li, Y., Huang, Q., Zhong, S., Wan, S. & Luo, L. (2024). Procyanidin alleviates ferroptosis and inflammation of LPS-induced RAW264. 7 cell via the Nrf2/HO-1 pathway. Naunyn-Schmiedeberg's Archives of Pharmacology, 397(6), 4055-4067.
  • Zhi, J., Yin, L., Zhang, Z., Lv, Y., Wu, F., Yang, Y., Zhang, E., Li, H., Lu, NÇ, Zhou, M., Hu, Q. (2024). Network pharmacology-based analysis of Jin-Si-Wei on the treatment of Alzheimer's disease. Journal of Ethnopharmacology, 319, 117291.
  • Zhou, J., Chen, G.B., Tang, Y.C., Sinha, R.A., Wu, Y., Yap, C.S., Wang, G., Hu, J., Xia, X., Tan, P., Goh, L.K., Yen, P.M. (2012). Genetic and bioinformatic analyses of the expression and function of PI3K regulatory subunit PIK3R3 in an Asian patient gastric cancer library. BMC Medical Genomics, 5, 1-8.
  • Zhu, X., Wang, Y., Ogawa, O., Lee, H. G., Raina, A.K., Siedlak, S.L., Harris, P.L.R., Fujioka, H., Shimohama, S., Tabaton, M., Atwood, C.S., Petersen, R.B., Perry, G., Smith, M. A. (2004). Neuroprotective properties of Bcl‐w in Alzheimer disease. Journal of Neurochemistry, 89(5), 1233-1240.

Alzheimer Hastalığı Tedavisinde Lignanlara Yönelik Ağ Farmakolojisi ve Moleküler Yerleştirme Perspektifleri

Year 2024, Volume: 27 Issue: Ek Sayı 1 (Suppl 1), 35 - 58

Seda Şirin , Serap Niğdelioğlu Dolanbay

https://doi.org/10.18016/ksutarimdoga.vi.1490753

Abstract

Alzheimer hastalığı (AH), sınırlı tedavi seçeneklerine sahip, zayıflatıcı nörodejeneratif bir durumdur. Çeşitli bitkilerde bulunan doğal olarak oluşan bir polifenol sınıfı olan lignanların, AH patolojisiyle ilişkili yolları modüle etme potansiyeline sahip olduğu gösterilmiştir. Bu çalışmada, hastalığın ilerlemesinde rol oynayan spesifik proteinleri hedefleyerek lignanların AH'ye karşı terapötik potansiyelini araştırmak için ağ farmakolojisi ve moleküler yerleştirme kullanılmıştır. Kurulan etkileşim ağımız EGFR, HSP90AA1, BCL2, HSP90AB1, IL6, JUN, ESR1, PIK3CA, ERBB2 ve PIK3R1 gibi önemli proteinleri içermektedir. Moleküler yerleştirme çalışmaları, lignanların bu proteinlerle nasıl etkileşime girdiğini ortaya çıkarmış ve inflamasyon modülasyonu, apoptoz düzenlemesi ve sinyal iletim yolları gibi mekanizmalar yoluyla AH'yi etkileme potansiyellerini vurgulamıştır. Sonuçlar, lignanların bu hedeflere önemli bağlanma yeteneklerine sahip olduğunu, potansiyel olarak aktivitelerini inhibe ettiğini ve dolayısıyla amiloid-beta birikimini ve tau fosforilasyonunu azaltarak AH semptomlarını hafiflettiğini göstermektedir. Bu bulgular, yeni AH tedavilerinin geliştirilmesi için bir temel olarak lignanların yaşayabilirliğini desteklemekte ve bunların etkinliğini ve güvenliğini doğrulamak için daha fazla in vivo çalışma yapılması çağrısında bulunmaktadır. Bu entegre yaklaşım, AH gibi karmaşık hastalıklara karşı yeni terapötik ajanların araştırılmasında ağ farmakolojisini ve moleküler yerleştirmeyi birleştirmenin değerini vurgulamaktadır.

Keywords

Alzheimer hastalığı Lignan Moleküler yerleştirme Ağ farmakolojisi

Ethical Statement

An ethics committee permission is not required for the article.

Supporting Institution

-

Project Number

-

Thanks

-

References

  • Abadi, A.M., Zaki, M.S.A., Sideeg, A.M., El, A.F., & Guo, X. (2024). Determination of cytotoxicity, biological effects and anti-human breast cancer properties of Bilobol. Iranian Journal of Chemistry and Chemical Engineering (IJCCE), 1, 1-24.
  • Abd El-Razek, M.H., Eissa, I.H., Al-Karmalawy, A.A., Elrashedy, A.A., El-Desoky, A.H., Aboelmagd, M., Mohamed, T.A., Hegazy, M.E.F. (2024). epi-Magnolin, a tetrahydrofurofuranoid lignan from the oleo-gum resin of Commiphora wightii, as inhibitor of pancreatic cancer cell proliferation, in-vitro and in-silico study. Journal of Biomolecular Structure and Dynamics, 1, 1-13.
  • Abdul, H., Butterfield, D. (2007). Involvement of PI3K/PKG/ERK1/2 signaling pathways in cortical neurons to trigger protection by cotreatment of acetyl-L-carnitine and alpha-lipoic acid against HNE-mediated oxidative stress and neurotoxicity: Implications for Alzheimer's disease. Free Radical Biology & Medicine, 42(3), 371-84.
  • Aguilar-Carrillo, Y., Soto-Urzúa, L., Martínez-Martínez, M.D.L.Á., Becerril-Ramírez, M., Martínez-Morales, L.J. (2024). Computational analysis of the tripartite interaction of phasins (PhaP4 and 5)-sigma factor (σ24)-DNA of Azospirillum brasilense Sp7. Polymers, 16(5), 611.
  • Ahsan, A., Ramanand, S., Whitehead, C., Hiniker, S., Rehemtulla, A., Pratt, W., Jolly, S., Gouveia, C., Truong, K., Waes, C., Ray, D., Lawrence, T., Nyati, M. (2012). Wild-type EGFR is stabilized by direct interaction with HSP90 in cancer cells and tumors. Neoplasia, 14(8),670-677 .
  • Alam, M., Ali, S., Mohammad, T., Hasan, G.M., Yadav, D.K., Hassan, M.I. (2021). B cell lymphoma 2: a potential therapeutic target for cancer therapy. International Journal of Molecular Sciences, 22(19), 10442.
  • Arjmandi-Rad, S., Vestergaard Nieland, J.D., Goozee, K.G., Vaseghi, S. (2024). The effects of different acetylcholinesterase inhibitors on EEG patterns in patients with Alzheimer’s disease: A systematic review. Neurological Sciences, 45(2), 417-430.
  • Astillero‐Lopez, V., Villar‐Conde, S., Gonzalez‐Rodriguez, M., Flores‐Cuadrado, A., Ubeda‐Banon, I., Saiz‐Sanchez, D., Martinez‐Marcos, A. (2024). Proteomic analysis identifies HSP90AA1, PTK2B, and ANXA2 in the human entorhinal cortex in Alzheimer's disease: Potential role in synaptic homeostasis and Aβ pathology through microglial and astroglial cells. Brain Pathology, e13235.
  • Atoki, A.V., Aja, P.M., Shinkafi, T.S., Ondari, E.N., Awuchi, C.G. (2023). Naringenin: its chemistry and roles in neuroprotection. Nutritional Neuroscience, 1, 1-30.
  • Austin, S., Katusic, Z. (2016). Loss of endothelial nitric oxide synthase promotes p25 generation and tau phosphorylation in a murine model of Alzheimer's disease. Circulation Research, 119(10), 1128-1134.
  • Behl, C., Hovey, L., Krajewski, S., Schubert, D., Reed, J. (1993). BCL-2 prevents killing of neuronal cells by glutamate but not by amyloid beta protein. Biochemical and Biophysical Research Communications, 197(2), 949-56.
  • Bindea, G., Mlecnik, B., Hackl, H., Charoentong, P., Tosolini, M., Kirilovsky, A., Fridman, W.H., Pages, F., Trajanoski, Z., Galon, J. (2009). ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks. Bioinformatics, 25(8), 1091-1093.
  • Birkinshaw, R. W., Gong, J. N., Luo, C. S., Lio, D., White, C. A., Anderson, M. A., Blombery, P., Lessene, G., Majewski, I. J., Thijssen, R., Roberts, A. W., Huang, D. C. S., Colman, P. M., & Czabotar, P. E. (2019). Structures of BCL-2 in complex with venetoclax reveal the molecular basis of resistance mutations. Nature Communications, 10(1), 2385.
  • Boada, M., Antunez, C., López-arrieta, J., Caruz, A., Moreno-Rey, C., Ramírez-Lorca, R., Morón, F., Hernández, I., Mauleon, A., Rosende-Roca, M., Martínez-Lage, P., Marín, J., Tárraga, L., Alegret, M., Pedrajas, J., Urda, N., Royo, J., Sáez, M., Gayán, J., Gonzáléz-Pérez, A., Real, L., Ruiz, A., Galán, J. (2012). Estrogen receptor alpha gene variants are associated with Alzheimer's disease. Neurobiology of Aging, 33, 198.e15-198.e24.
  • Bohush, A., Bieganowski, P., Filipek, A. (2019). Hsp90 and its co-chaperones in neurodegenerative diseases. International Journal of Molecular Sciences, 20(20), 4976.
  • Borsari, C., Keles, E., McPhail, J. A., Schaefer, A., Sriramaratnam, R., Goch, W., Schaefer, T., De Pascale, M., Bal, W., Gstaiger, M., Burke, J. E., & Wymann, M. P. (2022). Covalent Proximity Scanning of a Distal Cysteine to Target PI3Kα. Journal of the American Chemical Society, 144(14), 6326–6342.
  • Bredt, D., Ferris, C., Snyder, S. (1992). Nitric oxide synthase regulatory sites. Phosphorylation by cyclic AMP-dependent protein kinase, protein kinase C, and calcium/calmodulin protein kinase; identification of flavin and calmodulin binding sites. The Journal of Biological Chemistry, 267(16), 10976-81.
  • Casara, P., Davidson, J., Claperon, A., Le Toumelin-Braizat, G., Vogler, M., Bruno, A., Chanrion, M., Lysiak-Auvity, G., Le Diguarher, T., Starck, J. B., Chen, I., Whitehead, N., Graham, C., Matassova, N., Dokurno, P., Pedder, C., Wang, Y., Qiu, S., Girard, A. M., Schneider, E.,Grave, F., Studeny, A., Guasconi, G., Rocchetti, F., Maiga, S., Henlin, J.M., Colland, F., Kraus-Berthier, L., Le Gouill, S., Dyer, M.J.S., Hubbard, R., Wood, M., Amioti M., Cohen, G.M., Hickman, J.A., Morris, E., Murray, J., Geneste, O. (2018). S55746 is a novel orally active BCL-2 selective and potent inhibitor that impairs hematological tumor growth. Oncotarget, 9(28), 20075–20088.
  • Cedillo-Cortezano, M., Martinez-Cuevas, L.R., López, J.A.M., Barrera López, I.L., Escutia-Perez, S., Petricevich, V. L. (2024). Use of medicinal plants in the process of wound healing: A literature review. Pharmaceuticals, 17(3), 303.
  • Chen, L., Zhang, Y., Wang, S., Zhang, Y., Huang, T., Cai, Y. (2017). Prediction and analysis of essential genes using the enrichments of gene ontology and KEGG pathways. PLoS ONE, 12.
  • Chopade, A.R., Pol, R.P., Patil, P.A., Dharanguttikar, V.R., Naikwade, N.S., Dias, R.J., Mali, S.N. (2021). An insight into the anxiolytic effects of lignans (phyllanthin and hypophyllanthin) and tannin (corilagin) rich extracts of Phyllanthus amarus: An &in-silico and in-vivo approaches. Combinatorial Chemistry & High Throughput Screening, 24(3), 415-422.
  • Daina, A., Michielin, O., Zoete, V. (2014). iLOGP: a simple, robust, and efficient description of n-octanol/water partition coefficient for drug design using the GB/SA approach. Journal of Chemical Information and Modeling, 54(12), 3284-3301.
  • Daina, A., Michielin, O. (2016). A BOILED-Egg to predict gastrointestinal absorption and brain penetration of small molecules. ChemMedChem, 11(11), 1117-1121.
  • Daina, A., Michielin, O., Zoete, V. (2017). SwissADME: a free web tool to evaluate pharmacokinetics, drug-likeness and medicinal chemistry friendliness of small molecules. Scientific Reports, 7, 42717.
  • Dent, P., Booth, L., Roberts, J., Poklepovic, A., Cridebring, D., Reiman, E. (2021). Inhibition of heat shock proteins increases autophagosome formation, and reduces the expression of APP, Tau, SOD1 G93A and TDP-43. Aging, 13, 17097 - 17117.
  • Dissanayaka, D.S., Jayasena, V., Rainey-Smith, S.R., Martins, R.N., Fernando, W.B. (2024). The role of diet and gut microbiota in Alzheimer’s disease. Nutrients, 16(3), 412.
  • Eccles, S.A. (2011). The epidermal growth factor receptor/Erb-B/HER family in normal and malignant breast biology. The International Journal of Developmental Biology, 55(7-9), 685-96.
  • Eckert, A., Keil, U., Marques, C.A., Bonert, A., Frey, C., Schüssel, K., Müller, W.E. (2003). Mitochondrial dysfunction, apoptotic cell death, and Alzheimer’s disease. Biochemical Pharmacology, 66(8), 1627-1634.
  • Fakhri, S., Iranpanah, A., Gravandi, M. M., Moradi, S. Z., Ranjbari, M., Majnooni, M. B., Echeverria, J., Qi, Y., Wang, M., Liao, P., Farzaei, M.H., Xiao, J. (2021). Natural products attenuate PI3K/Akt/mTOR signaling pathway: A promising strategy in regulating neurodegeneration. Phytomedicine, 91, 153664.
  • Franceschini, A., Lin, J., von Mering, C., Jensen, L.J. (2016). SVD-phy: improved prediction of protein functional associations through singular value decomposition of phylogenetic profiles. Bioinformatics, 32(7), 1085-1087.
  • Franceschini, A., Szklarczyk, D., Frankild, S., Kuhn, M., Simonovic, M., Roth, A., Lin, J., Minguez, P., Bork, P., von Mering, C., Jensen, L.J. (2012). STRING v9. 1: protein-protein interaction networks, with increased coverage and integration. Nucleic Acids Research, 41(D1), D808-D815.
  • Fraser, M., Bayazitov, I., Zakharenko, S., Baker, S. (2008). Phosphatase and tensin homolog, deleted on chromosome 10 deficiency in brain causes defects in synaptic structure, transmission and plasticity, and myelination abnormalities. Neuroscience, 151, 476-488.
  • Ge, S.X., Jung, D., Yao, R. (2020). ShinyGO: a graphical gene-set enrichment tool for animals and plants Bioinformatics, 36, 2628–2629.
  • Gene Ontology Consortium (2017). Expansion of the Gene Ontology knowledgebase and resources. Nucleic Acids Research, 45, D331 - D338.
  • Gobom, J., Brinkmalm, A., Brinkmalm, G., Blennow, K., Zetterberg, H. (2024). Alzheimer's disease biomarker analysis using targeted mass spectrometry. Molecular & Cellular Proteomics, 23(2),100721.
  • Gong, C., Iqbal, K. (2008). Hyperphosphorylation of microtubule-associated protein tau: a promising therapeutic target for Alzheimer disease. Current Medicinal Chemistry, 15(23), 2321-2328.
  • Gonzalez-Rodriguez, M., Villar-Conde, S., Astillero-Lopez, V., Villanueva-Anguita, P., Ubeda-Banon, I., Flores-Cuadrado, A., Martinez-Marcos, A., Saiz-Sanchez, D. (2021). Neurodegeneration and Astrogliosis in the Human CA1 Hippocampal Subfield Are Related to hsp90ab1 and bag3 in Alzheimer’s Disease. International Journal of Molecular Sciences, 23(1), 165.
  • Hernández, P., Lee, G., Sjoberg, M., Maccioni, R.B. (2009). Tau phosphorylation by cdk5 and Fyn in response to amyloid peptide Aβ (25-35): involvement of lipid rafts. Journal of Alzheimer's Disease, 16(1), 149-156.
  • Hoang, S.H., Lam, E.M., Dao, H. (2024). Computational assessment of gut microbiota metabolite enterolactone as a promising Aβ42 inhibitor in Alzheimer's disease. DYSONA-Life Science, 5(1), 9-20.
  • Hopkins, A.L. (2007). Network pharmacology: The next paradigm in drug discovery. Nature Chemical Biology, 3(11), 682-690.
  • Hoxhaj, G., Manning, B.D. (2020). The PI3K–AKT network at the interface of oncogenic signalling and cancer metabolism. Nature Reviews Cancer, 20(2), 74-88.
  • Hoter, A., El-Sabban, M.E., Naim, H.Y. (2018). The HSP90 family: structure, regulation, function, and implications in health and disease. International Jurnal of Molecular Sciences, 19(9), 2560.
  • Huang, D.W., Sherman, B.T., Lempicki, R.A. (2009). Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nature Protocols, 4(1), 44-57.
  • Ibrahim, M., Uzairu, A., Shallangwa, G., & Uba, S. (2020). In-silico activity prediction and docking studies of some 2, 9-disubstituted 8-phenylthio/phenylsulfinyl-9h-purine derivatives as Anti-proliferative agents. Heliyon, 6(1), e03158.
  • Ibrahim, M.T., Uzairu, A., Uba, S., Shallangwa, G.A. (2020). Computational modeling of novel quinazoline derivatives as potent epidermal growth factor receptor inhibitors. Heliyon, 6(2), e03289.
  • Jayaswamy, P.K., Vijaykrishnaraj, M., Patil, P., Alexander, L.M., Kellarai, A., Shetty, P. (2023). Implicative role of epidermal growth factor receptor and its associated signaling partners in the pathogenesis of Alzheimer’s disease. Ageing Research Reviews, 83, 101791.
  • Jensen, L.J., Kuhn, M., Stark, M., Chaffron, S., Creevey, C., Muller, J., Doerks, T., Julien, P., Roth, A., Simonovic, M., Bork, P., von Mering, C. (2009). STRING 8—a global view on proteins and their functional interactions in 630 organisms. Nucleic Acids Research, 37(suppl_1), D412-D416.
  • Jimenez, S., Torres, M., Vizuete, M., Sanchez-Varo, R., Sanchez-Mejias, E., Trujillo-Estrada, L., Carmona-Cuenca, I., Caballero, C., Ruano, Gutierrez, A., Vitorica, J. (2011). Age-dependent accumulation of soluble amyloid β (Aβ) oligomers reverses the neuroprotective effect of soluble amyloid precursor protein-α (sAPPα) by modulating phosphatidylinositol 3-kinase (PI3K)/Akt-GSK-3β pathway in Alzheimer mouse model. Journal of Biological Chemistry, 286(21), 18414-18425.
  • Kumar, M., Bansal, N. (2022). Implications of phosphoinositide 3-kinase-Akt (PI3K-Akt) pathway in the pathogenesis of Alzheimer’s disease. Molecular Neurobiology, 59(1), 354-385.
  • Kummer, K.K., Zeidler, M., Kalpachidou, T., Kress, M. (2021). Role of IL-6 in the regulation of neuronal development, survival and function. Cytokine, 144, 155582.
  • Lan, Y.L., Zhao, J., Li, S. (2015). Update on the neuroprotective effect of estrogen receptor alpha against Alzheimer's disease. Journal of Alzheimer's Disease, 43(4), 1137-1148.
  • Ledonne, A., Mango, D., Latagliata, E.C., Chiacchierini, G., Nobili, A., Nisticò, R., D’Amelio, M., Puglisi-Allegra, S., Mercuri, N.B. (2018). Neuregulin 1/ErbB signalling modulates hippocampal mGluRI-dependent LTD and object recognition memory. Pharmacological Research, 130, 12-24.
  • Lee, K.H., Lee, S.J., Lee, H.J., Choi, G., Jung, Y., Kim, D.I., Gabr, A., Ryu, J.M., Han, H. (2017). Amyloid β1-42 (Aβ1-42) induces the CDK2-mediated phosphorylation of tau through the activation of the mTORC1 signaling pathway while promoting neuronal cell death. Frontiers in Molecular Neuroscience, 10.
  • Lei, S., Wu, S., Wang, G., Li, B., Liu, B., Lei, X. (2021). Pinoresinol diglucoside attenuates neuroinflammation, apoptosis and oxidative stress in a mice model with Alzheimer’s disease. Neuroreport, 32(3), 259-267.
  • Li, B., Ma, W., Jaffe, H., Zheng, Y., Takahashi, S., Zhang, L., Kulkarni, A., Pant, H. (2003). Cyclin-dependent kinase-5 is involved in neuregulin-dependent activation of phosphatidylinositol 3-kinase and Akt activity mediating neuronal survival. Journal of Biological Chemistry, 278, 35702-35709.
  • Li, S., Zhang, B., Zhang, N., Zhang, Y. (2011). Network pharmacology: a new approach for chinese herbal medicine research. Evidence-Based Complementary and Alternative Medicine, 2011.
  • Liebermann, D.A., Gregory, B., Hoffman, B. (1998). AP-1 (Fos/Jun) transcription factors in hematopoietic differentiation and apoptosis. International Journal of Oncology, 12(3), 685-1385.
  • Liu, J., Yuan, S., Niu, X., Kelleher, R., Sheridan, H. (2022b). ESR1 dysfunction triggers neuroinflammation as a critical upstream causative factor of the Alzheimer’s disease process. Aging, 14, 8595-8614.
  • Liu, Y., Yang, X., Gan, J., Chen, S., Xiao, Z.X., Cao, Y. (2022a). CB-Dock2: Improved protein–ligand blind docking by integrating cavity detection, docking and homologous template fitting. Nucleic Acids Research, 50(W1), W159-W164.
  • Lu, C., Fu, W., Zhao, D., Mattson, M. P. (2002). The DNA damaging agent etoposide activates a cell survival pathway involving α‐amino‐3‐hydroxy‐5‐methylisoxazole‐4‐propionate receptors and mitogen‐activated protein kinases in hippocampal neurons. Journal of Neuroscience Research, 70(5), 671-679.
  • Lyra e Silva, N.M., Gonçalves, R.A., Pascoal, T.A., Lima-Filho, R.A., Resende, E.D.P.F., Vieira, E.L., Texeira, A.L., de Souza, L.C., Peny, J.A., Fortuna, J.T.S., Furigo, I.C., Hashiguchi, D., Miya-Coreixas, V.S., Clarke, J.R., Abisambrai J.F., Longo, B.M., Donato Jr, J., Eraser, P.E., Rosa-Neto, P., Caramelli, P., Ferreira, S.T., De Felice, F.G. (2021). Pro-inflammatory interleukin-6 signaling links cognitive impairments and peripheral metabolic alterations in Alzheimer’s disease. Translational Psychiatry, 11(1), 251.
  • Maiese, K., Chong, Z.Z. (2004). Insights into oxidative stress and potential novel therapeutic targets for Alzheimer disease. Restorative Neurology and Neuroscience, 22(2), 87-104.
  • Majahan, A., Sharma, N., Ulhe, A., Patil, R., Hegde, M., Mali, A. (2024). From dietary lignans to cancer therapy: Integrative systems analysis of enterolactone's molecular targets and signaling pathways in combatting cancer stem cells in triple-negative breast cancer. Food Bioscience, 58(5-6), 103732.
  • Martini, M., De Santis, M.C., Braccini, L., Gulluni, F., Hirsch, E. (2014). PI3K/AKT signaling pathway and cancer: an updated review. Annals of Medicine, 46(6), 372-383.
  • Maximov, P. Y., Abderrahman, B., Fanning, S. W., Sengupta, S., Fan, P., Curpan, R. F., Rincon, D. M. Q., Greenland, J. A., Rajan, S. S., Greene, G. L., & Jordan, V. C. (2018). Endoxifen, 4-Hydroxytamoxifen and an estrogenic derivative modulate estrogen receptor complex mediated apoptosis in breast cancer. Molecular Pharmacology, 94(2), 812–822.
  • Miller, M. S., Maheshwari, S., McRobb, F. M., Kinzler, K. W., Amzel, L. M., Vogelstein, B., & Gabelli, S. B. (2017). Identification of allosteric binding sites for PI3Kα oncogenic mutant specific inhibitor design. Bioorganic & medicinal chemistry, 25(4), 1481–1486.
  • Miron, J., Picard, C., Frappier, J., Dea, D., Théroux, L., Poirier, J. (2018). TLR4 gene expression and pro-inflammatory cytokines in Alzheimer's sisease and in response to hippocampal deafferentation in rodents. Journal of Alzheimer's disease: JAD, 63(4), 1547-1556.
  • Mishra, S., Dahima, R. (2019). In vitro ADME studies of TUG-891, a GPR-120 inhibitor using SWISS ADME predictor. Journal of Drug Delivery and Therapeutics, 9(2-s), 366-369.
  • Mohammadi, M.K., Firuzi, O., Khoshneviszadeh, M., Razzaghi-Asl, N., Sepehri, S., & Miri, R. (2014). Novel 9-(alkylthio)-Acenaphtho[1,2-e]-1,2,4-triazine derivatives: synthesis, cytotoxic activity and molecular docking studies on B-cell lymphoma 2 (Bcl-2). DARU Journal of Pharmaceutical Sciences, 22, 1-11.
  • Muchtaridi, M., Syahidah, H. N., Subarnas, A., Yusuf, M., Bryant, S. D., & Langer, T. (2017). Molecular docking and 3D-pharmacophore modeling to study the interactions of chalcone derivatives with estrogen receptor alpha. Pharmaceuticals, 10(4), 81.
  • Munkley, J., Livermore, K. E., McClurg, U. L., Kalna, G., Knight, B., McCullagh, P., McGrath, J., Crundwell, M., Leung, H.Y., Robson, C.N., Harries, L.W., Rajan, P., Elliott, D. J. (2015). The PI3K regulatory subunit gene PIK3R1 is under direct control of androgens and repressed in prostate cancer cells. Oncoscience, 2(9), 755.
  • Murray, J. B., Davidson, J., Chen, I., Davis, B., Dokurno, P., Graham, C. J., Harris, R., Jordan, A., Matassova, N., Pedder, C., Ray, S., Roughley, S. D., Smith, J., Walmsley, C., Wang, Y., Whitehead, N., Williamson, D. S., Casara, P., Le Diguarher, T., Hickman, J., Stark, J., Kotschy, A., Geneste, O., Hubbard, R. E. (2019). Establishing Drug Discovery and Identification of Hit Series for the Anti-apoptotic Proteins, Bcl-2 and Mcl-1. ACS Omega, 4(5), 8892–8906.
  • Nag, A., Verma, P., Paul, S., Kundu, R. (2022). In silico analysis of the apoptotic and HPV inhibitory roles of some selected phytochemicals detected from the rhizomes of greater cardamom. Applied Biochemistry and Biotechnology, 194(10), 4867-4891.
  • Nawfetrias, W., Devy, L., Esyanti, R.R., Faizal, A. (2024). Phyllanthus lignans: A review of biological activity and elicitation. Horticulturae, 10(2), 195.
  • Oliveira, J., Costa, M., Almeida, M., Silva, O., Henriques, A. (2017). Protein phosphorylation is a key mechanism in Alzheimer's disease. Journal of Alzheimer's disease: JAD, 58(4), 953-978.
  • Oliveira Silva, R., Counil, H., Rabanel, J.M., Haddad, M., Zaouter, C., Ben Khedher, M. R., Patten, S.A., Ramassamy, C. (2024). Donepezil-loaded nanocarriers for the treatment of Alzheimer’s disease: Superior efficacy of extracellular vesicles over polymeric nanoparticles. International Journal of Nanomedicine, 1077-1096.
  • Ou, G.Y., Lin, W.W., Zhao, W.J. (2021). Neuregulins in neurodegenerative diseases. Frontiers in Aging Neuroscience, 13, 662474.
  • Parihar, M.S., Brewer, G.J. (2010). Amyloid-β as a modulator of synaptic plasticity. Journal of Alzheimer's Disease, 22(3), 741-763.
  • Park, J. H., Liu, Y., Lemmon, M. A., & Radhakrishnan, R. (2012). Erlotinib binds both inactive and active conformations of the EGFR tyrosine kinase domain. Biochemical Journal, 448(Pt 3), 417.
  • Park, K.W. (2024). Anti-amyloid Antibody Therapies for Alzheimer’s Disease. Nuclear Medicine and Molecular Imaging, 1-10.
  • Pattar, S. V., Adhoni, S. A., Kamanavalli, C. M., & Kumbar, S. S. (2020). In silico molecular docking studies and MM/GBSA analysis of coumarin-carbonodithioate hybrid derivatives divulge the anticancer potential against breast cancer. Beni-Suef University Journal of Basic and Applied Sciences, 9, 1-10.
  • Paul, D., Mahanta, S., Tag, H., Das, S.K., Das Gupta, D., Tanti, B., Ananthan, R., Das, R., Jambhulkar, S. & Hui, P.K. (2021). Identification of tyrosine kinase inhibitors from Panax bipinnatifidus and Panax pseudoginseng for RTK—HER2 and VEGFR2 receptors, by in silico approach. Molecular Diversity, 1-23.
  • Pike, C.J. (2017). Sex and the development of Alzheimer's disease. Journal of Neuroscience Research, 95(1-2), 671-680.
  • Prete, D., Rice, R., Rajadhyaksha, A., D’Adamio, L. (2016). Amyloid precursor protein (APP) may act as a substrate and a recognition unit for CRL4CRBN and Stub1 E3 ligases facilitating ubiquitination of proteins involved in presynaptic functions and neurodegeneration. The Journal of Biological Chemistry, 291, 17209-17227.
  • Qin, Y., Yang, P., He, W., Li, D., Zeng, L., Li, J., Zhou, T., Peng, J., Cao, L., Huang, W. (2024). Novel histone post-translational modifications in Alzheimer’s disease: current advances and implications. Clinical Epigenetics, 16(1), 39.
  • Qu, W.S., Liu, J.L., Li, C.Y., Li, X., Xie, M.J., Wang, W., Tian, D.S. (2015). Rapidly activated epidermal growth factor receptor mediates lipopolysaccharide-triggered migration of microglia. Neurochemistry international, 90, 85-92.
  • Quiroga, R., Villarreal, M.A. (2016). Vinardo: A scoring function based on autodock vina improves scoring, docking, and virtual screening. PloS One, 11(5), e0155183.
  • Rajmohan, R., Reddy, P.H. (2017). Amyloid-beta and phosphorylated tau accumulations cause abnormalities at synapses of Alzheimer’s disease neurons. Journal of Alzheimer's Disease, 57(4), 975-999.
  • Razani, E., Pourbagheri-Sigaroodi, A., Safaroghli-Azar, A., Zoghi, A., Shanaki-Bavarsad, M., Bashash, D. (2021). The PI3K/Akt signaling axis in Alzheimer’s disease: a valuable target to stimulate or suppress?. Cell Stress and Chaperones, 26(6), 871-887.
  • Reddy, V. P., Aryal, P., Robinson, S., Rafiu, R., Obrenovich, M., Perry, G. (2020). Polyphenols in Alzheimer’s disease and in the gut–brain axis. Microorganisms, 8(2), 199.
  • Roe, S. M., Prodromou, C., O'Brien, R., Ladbury, J. E., Piper, P. W., & Pearl, L. H. (1999). Structural basis for inhibition of the Hsp90 molecular chaperone by the antitumor antibiotics radicicol and geldanamycin. Journal of Medicinal Chemistry, 42(2), 260–266.
  • Rubio-Perez, J.M., Morillas-Ruiz, J.M. (2012). A review: Inflammatory process in Alzheimer's disease, role of cytokines. The Scientific World Journal, 2012(1), 756357.
  • Russell, J.K., Jones, C.K., Newhouse, P.A. (2019). The role of estrogen in brain and cognitive aging. Neurotherapeutics, 16(3), 649-665.
  • Salminen, A., Kauppinen, A., Suuronen, T., Kaarniranta, K., Ojala, J. (2009). ER stress in Alzheimer's disease: a novel neuronal trigger for inflammation and Alzheimer's pathology. Journal of Neuroinflammation, 6, 1-13.
  • Sato, K., Takayama, K.I., Inoue, S. (2023). Expression and function of estrogen receptors and estrogen-related receptors in the brain and their association with Alzheimer’s disease. Frontiers in Endocrinology, 14, 1220150.
  • Scorrano, L., Korsmeyer, S.J. (2003). Mechanisms of cytochrome c release by proapoptotic BCL-2 family members. Biochemical and Biophysical Research Communications, 304(3), 437-444.
  • Shacka, J.J., Roth, K.A. (2005). Regulation of neuronal cell death and neurodegeneration by members of the Bcl-2 family: therapeutic implications. Current Drug Targets-CNS & Neurological Disorders, 4(1), 25-39.
  • Sharma, S., & Kumar, P. (2023). Deciphering the molecular mechanism of HSP90AB1 as a potential heat shock protein and understanding the role of alkaloids in the therapeutic suppression of glioblastomas (GBMs). In 2023 3rd International Conference on Innovative Sustainable Computational Technologies (CISCT) (pp. 1-5). IEEE.
  • Shaw, S., Bourne, T., Meier, C., Carrington, B., Gelinas, R., Henry, A., Popplewell, A., Adams, R., Baker, T., Rapecki, S., Marshall, D., Moore, A., Neale, H., & Lawson, A. (2014). Discovery and characterization of olokizumab: a humanized antibody targeting interleukin-6 and neutralizing gp130-signaling. mAbs, 6(3), 774–782.
  • Shtaiwi, A., Adnan, R., Khairuddean, M., & Khan, S. U. (2019). Computational investigations of the binding mechanism of novel benzophenone imine inhibitors for the treatment of breast cancer. RSC Advances, 9(61), 35401-35416.
  • Snel, B., Lehmann, G., Bork, P., & Huynen, M. A. (2000). STRING: a web-server to retrieve and display the repeatedly occurring neighbourhood of a gene. Nucleic Acids Research, 28(18), 3442-3444.
  • Sontag, J., Sontag, E. (2014). Protein phosphatase 2A dysfunction in Alzheimer’s disease. Frontiers in Molecular Neuroscience, 7, 16.
  • Souza, D.C.S., Costa‐Silva, T.A., Morais, T.R., Brito, J.R., Ferreira, E.A., Antar, G.M., Sartorelli, P., Tempone, A.G., Lago, J.H.G. (2021). Simplified derivatives of dibenzylbutyrolactone lignans from Hydrocotyle bonariensis as antitrypanosomal candidates. Chemistry & Biodiversity, 18(10), e2100515.
  • Stebbins, C. E., Russo, A. A., Schneider, C., Rosen, N., Hartl, F. U., & Pavletich, N. P. (1997). Crystal structure of an Hsp90-geldanamycin complex: targeting of a protein chaperone by an antitumor agent. Cell, 89(2), 239–250.
  • Sundermann, E.E., Maki, P.M., Bishop, J.R. (2010). A review of estrogen receptor α gene (ESR1) polymorphisms, mood, and cognition. Menopause, 17(4), 874-886.
  • Szklarczyk, D., Franceschini, A., Kuhn, M., Simonovic, M., Roth, A., Minguez, P., Doerks, T., Stark, M., Muller, J., Bork, P., Jensen, L.J., Mering, C.V. (2010). The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Research, 39(suppl_1), D561-D568.
  • Szklarczyk, D., Franceschini, A., Wyder, S., Forslund, K., Heller, D., Huerta-Cepas, J., Simonovic, M., Roth, A., Santos, A., Tsafou, K.P., Kuhn, M., Bork, P., Jensen, L.J., Von Mering, C. (2015). STRING v10: protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Research, 43(D1), D447-D452.
  • Szklarczyk, D., Gable, A. L., Lyon, D., Junge, A., Wyder, S., Huerta-Cepas, J., Simonovic, M., Doncheva, N.T., Morris, J.H., Bork, P., Jensen, L.J. Mering, C.V. (2019). STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Research, 47(D1), D607-D613.
  • Szklarczyk, D., Kirsch, R., Koutrouli, M., Nastou, K., Mehryary, F., Hachilif, R., Annika, G.L., Fang, T., Doncheva, N.T., Pyysalo, S., Bork, P., Jensen, L.J., von Mering, C. (2023). The STRING database in 2023: protein–protein association networks and functional enrichment analyses for any sequenced genome of interest. Nucleic Acids Research, 51(D1), D638-D646.
  • Szklarczyk, D., Morris, J.H., Cook, H., Kuhn, M., Wyder, S., Simonovic, M., Santos, A., Doncheva, N.T., Roth, A., Bork, P., Jensen, L.J., Von Mering, C. (2016). The STRING database in 2017: quality-controlled protein–protein association networks, made broadly accessible. Nucleic Acids Research, 45, D362-68.
  • Tavassoly, O., Sato, T., Tavassoly, I. (2020). Inhibition of brain epidermal growth factor receptor activation: a novel target in neurodegenerative diseases and brain injuries. Molecular Pharmacology, 98(1), 13-22.
  • Thangavel, N., Al Bratty, M., Al Hazmi, H.A., Najmi, A., Ali Alaqi, R.O. (2021). Molecular docking and molecular dynamics aided virtual search of OliveNet™ Directory for Secoiridoids to combat SARS-CoV-2 infection and associated hyperinflammatory responses. Frontiers in Molecular Biosciences, 7, 627767.
  • Ugurlu, S.Y., McDonald, D., Lei, H., Jones, A.M., Li, S., Tong, H.Y., Butler, M.S., He, S. (2024). Cobdock: an accurate and practical machine learning-based consensus blind docking method. Journal of Cheminformatics, 16(1), 5.
  • URL1 https://cadd.labshare.cn/cb-dock2/index.php
  • URL2 https://www.rcsb.org/structure/3UG2
  • URL3 https://www.rcsb.org/structure/4HJO
  • URL4 https://www.rcsb.org/structure/1XKK
  • URL5 https://www.rcsb.org/structure/1yet
  • URL6 https://www.rcsb.org/structure/1yes
  • URL7 https://www.rcsb.org/structure/1BGQ
  • URL8 https://www.rcsb.org/structure/6qgg
  • URL9 https://www.rcsb.org/structure/6O0K
  • URL10 https://www.rcsb.org/structure/6GL8
  • URL11 https://www.rcsb.org/structure/4CNI
  • URL12 https://www.rcsb.org/structure/5w9c
  • URL13 https://www.rcsb.org/structure/7R9V
  • URL14 https://www.rcsb.org/structure/5SX8
  • URL15 https://www.intechopen.com/chapters/75508
  • URL16 http://zhanggroup.org/BioLiP2/pdb/single/ 1E7U
  • URL17 http://zhanggroup.org/BioLiP2/pdb/single/ 1E7V
  • URL18 http://zhanggroup.org/BioLiP2/pdb/single/ 1E7W
  • Von Mering, C., Huynen, M., Jaeggi, D., Schmidt, S., Bork, P., Snel, B. (2003). STRING: a database of predicted functional associations between proteins. Nucleic Acids Research, 31(1), 258-261.
  • Von Mering, C., Jensen, L. J., Kuhn, M., Chaffron, S., Doerks, T., Krüger, B., Snel, B., Bork, P. (2007). STRING 7—recent developments in the integration and prediction of protein interactions. Nucleic Acids Research, 35(suppl_1), D358-D362.
  • Von Mering, C., Jensen, L. J., Snel, B., Hooper, S. D., Krupp, M., Foglierini, M., Jouffre, N., Huynen, M.A., Bork, P. (2005). STRING: known and predicted protein–protein associations, integrated and transferred across organisms. Nucleic Acids Research, 33(suppl_1), D433-D437.
  • Wang, B.J., Her, G.M., Hu, M.K., Chen, Y.W., Tung, Y.T., Wu, P.Y., Hsu, W.M., Lee, H., Jin, L.W., Hwang, S.P.L., Chen, R.P.Y., Huang, C.J., Liao, Y.F. (2017). ErbB2 regulates autophagic flux to modulate the proteostasis of APP-CTFs in Alzheimer’s disease. Proceedings of the National Academy of Sciences, 114(15), E3129-E3138.
  • Webers, A., Heneka, M.T., Gleeson, P.A. (2020). The role of innate immune responses and neuroinflammation in amyloid accumulation and progression of Alzheimer's disease. Immunology and Cell Biology, 98(1), 28-41.
  • Weinkove, D., Bastiani, M., Chessa, T., Joshi, D., Hauth, L., Cooke, F., Divecha, N., Schuske, K. (2008). Overexpression of PPK-1, the Caenorhabditis elegans Type I PIP kinase, inhibits growth cone collapse in the developing nervous system and causes axonal degeneration in adults. Developmental Biology, 313(1), 384-97 .
  • Weisman, D., Hakimian, E., Ho, G.J. (2006). Interleukins, inflammation, and mechanisms of Alzheimer's disease. Vitamins & Hormones, 74, 505-530.
  • Wood, E. R., Truesdale, A. T., McDonald, O. B., Yuan, D., Hassell, A., Dickerson, S. H., Ellis, B., Pennisi, C., Horne, E., Lackey, K., Alligood, K.J., Rusnak, D.W., Gilmer, T.M. & Shewchuk, L. (2004). A unique structure for epidermal growth factor receptor bound to GW572016 (Lapatinib) relationships among protein conformation, inhibitor off-rate, and receptor activity in tumor cells. Cancer Research, 64(18), 6652-6659.
  • Wu, L., Xiong, X., Wu, X., Ye, Y., Jian, Z., Zhi, Z., Gu, L. (2020). Targeting oxidative stress and inflammation to prevent ischemia-reperfusion injury. Frontiers in Molecular Neuroscience, 13, 28.
  • Xie, C., Mao, X., Huang, J., Ding, Y., Wu, J., Dong, S., Kong, L., Gao, G., Li, C.Y., Wei, L. (2011). KOBAS 2.0: a web server for annotation and identification of enriched pathways and diseases. Nucleic Acids Research, 39(suppl_2), W316-W322.
  • Xing, Z., Chu, C., Chen, L., Kong, X. (2016). The use of Gene Ontology terms and KEGG pathways for analysis and prediction of oncogenes. Biochimica et Biophysica Acta, 1860(11),2725-34.
  • Xu, S., Li, X., Liu, S., Tian, P., Li, D. (2022). Juniperus sabina L. as a source of Podophyllotoxins: Extraction optimization and anticholinesterase activities. International Journal of Molecular Sciences, 23(18), 10205.
  • Yang, X., Liu, Y., Gan, J., Xiao, Z.X., Cao, Y. (2022). FitDock: Protein–ligand docking by template fitting. Briefings in Bioinformatics, 23(3), bbac087.
  • Yarza, R., Vela, S., Solas, M., Ramirez, M.J. (2016). c-Jun N-terminal kinase (JNK) signaling as a therapeutic target for Alzheimer’s disease. Frontiers in Pharmacology, 6, 321.
  • Yoshikawa, S., Kukimoto-Niino, M., Parker, L., Handa, N., Terada, T., Fujimoto, T., Terazawa, Y., Wakiyama, M., Sato, M., Sano, S., Kobayashi, T., Tanaka, T., Chen, L., Liu, Z-J., Wang, B-C., Shirouzu, M., Kawa, S., Semba, K., Yamamoto, T., & Yokoyama, S. (2013). Structural basis for the altered drug sensitivities of non-small cell lung cancer-associated mutants of human epidermal growth factor receptor. Oncogene, 32(1), 27-38.
  • Zeng, J., Weng, Y., Lai, T., Chen, L., Li, Y., Huang, Q., Zhong, S., Wan, S. & Luo, L. (2024). Procyanidin alleviates ferroptosis and inflammation of LPS-induced RAW264. 7 cell via the Nrf2/HO-1 pathway. Naunyn-Schmiedeberg's Archives of Pharmacology, 397(6), 4055-4067.
  • Zhi, J., Yin, L., Zhang, Z., Lv, Y., Wu, F., Yang, Y., Zhang, E., Li, H., Lu, NÇ, Zhou, M., Hu, Q. (2024). Network pharmacology-based analysis of Jin-Si-Wei on the treatment of Alzheimer's disease. Journal of Ethnopharmacology, 319, 117291.
  • Zhou, J., Chen, G.B., Tang, Y.C., Sinha, R.A., Wu, Y., Yap, C.S., Wang, G., Hu, J., Xia, X., Tan, P., Goh, L.K., Yen, P.M. (2012). Genetic and bioinformatic analyses of the expression and function of PI3K regulatory subunit PIK3R3 in an Asian patient gastric cancer library. BMC Medical Genomics, 5, 1-8.
  • Zhu, X., Wang, Y., Ogawa, O., Lee, H. G., Raina, A.K., Siedlak, S.L., Harris, P.L.R., Fujioka, H., Shimohama, S., Tabaton, M., Atwood, C.S., Petersen, R.B., Perry, G., Smith, M. A. (2004). Neuroprotective properties of Bcl‐w in Alzheimer disease. Journal of Neurochemistry, 89(5), 1233-1240.
There are 150 citations in total.

Details

Primary Language English
Subjects Pharmaceutical Botany
Journal Section RESEARCH ARTICLE
Authors

Seda Şirin 0000-0003-2636-725X

Serap Niğdelioğlu Dolanbay 0000-0002-1238-0894

Project Number -
Early Pub Date September 15, 2024
Publication Date
Submission Date May 27, 2024
Acceptance Date August 14, 2024
Published in Issue Year 2024Volume: 27 Issue: Ek Sayı 1 (Suppl 1)

Cite

APA Şirin, S., & Niğdelioğlu Dolanbay, S. (2024). Network Pharmacology and Molecular Docking Perspectives into Lignans for Alzheimer’s Disease Treatment. Kahramanmaraş Sütçü İmam Üniversitesi Tarım Ve Doğa Dergisi, 27(Ek Sayı 1 (Suppl 1), 35-58. https://doi.org/10.18016/ksutarimdoga.vi.1490753
 Download Cover Image


International Peer Reviewed Journal
Free submission and publication
Published 6 times a year



88x31.png


KSU Journal of Agriculture and Nature

e-ISSN: 2619-9149