In silico approach in treatment of alzheimer disease of apolipoprotein e4 inhibitor discovery
DOI:
https://doi.org/10.71727/disciplinares.v2i4.137Palabras clave:
Apo lipoprotein, Alzheimer’s disease, docking, bioinformatics, Digit toxin digitoxosideResumen
Un importante factor de riesgo genético de la enfermedad de Alzheimer es la presencia de apolipoproteína E4 (Apoe) (AD). Mantener un suministro constante de lípidos neuronales para la producción rápida y dinámica de membranas es esencial para la función cerebral. El desarrollo de placas beta amiloides (A) y ovillos neurofibrilares en el cerebro es lo que causa la EA. El objetivo de la investigación actual es prever un tratamiento contra la actividad excesiva de la apoE4. La presente investigación incluyó 22 sustancias químicas naturales, entre ellas derivados marinos, microbianos y vegetales, que se utilizaron como inhibidores para bloquear la acción de la proteína apoE4. También se acoplaron seis compuestos sintéticos a la proteína diana con el fin de comparar y evaluar los resultados con los productos químicos naturales. Teleglobe, un producto químico sintético, mostró la mayor afinidad de unión con la proteína diana, pero no mostró enlaces de hidrógeno con ninguno de los residuos de aminoácidos. Además, una sustancia natural denominada digitoxina digitoxósido presentó la mayor afinidad de unión, pero no formó enlaces de hidrógeno con ninguno de los residuos de aminoácidos. Basándonos en la afinidad de unión y los enlaces de hidrógeno para disminuir el desarrollo de la EA, nuestra investigación identificó el digitoxina digitoxósido como posible sustancia química principal.
Citas
Wimo, A.; Jönsson, L.; Bond, J.; Prince, M.; Winblad, B., The worldwide economic impact of dementia 2010. Alzheimers Dement., (N Y), 2013, 9(1), 1-11. e3.
Huang, H.-J.; Chen, H.-Y.; Lee, C.-C.; Chen, C.Y.-C. Computational design of apolipoprotein E4 inhibitors for Alzheimer’s disease therapy from traditional Chinese medicine. BioMed Res. Int., 2014, 2014.
Gómez-Isla,T.; Hollister, R.; West, H.; Mui, S.; Growdon, J. H.; Petersen, R. C.; Parisi, J. E.; Hyman, B.T. Neuronal loss correlates with but exceeds ApoE4 Inhibitor for Alzheimer’s Disease Therapy Current Computer-Aided Drug Design, 2019, Vol.(b)15, No. 1 103 neurofibrillary tangles in Alzheimer's disease. Annals Neurol., 1997, 41(1), 17-24.
Corder, E.H.; Saunders, A.M.; Strittmatter, W.J.; Schmechel, D.E.; Gaskell, P.C.; Small, G.; Roses, A.D.; Haines, J.; Pericak-Vance, M.A. Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer's disease in late onset families. Science, 1993, 261(5123), 921-923.
Pericak-Vance, M.; Bebout, J.; Gaskell, P.; Yamaoka, L.; Hung, W.-Y.; Alberts, M.; Walker, A.; Bartlett, R.; Haynes, C.; Welsh, K., Linkage studies in familial Alzheimer disease: evidence for chromosome 19 linkage. Am. Journal Human Gen., 1991, 48(6), 1034.
Johnson, L.A.; Olsen, R.H.; Merkens, L.S.; DeBarber, A.; Steiner, R.D.; Sullivan, P.M.; Maeda, N.; Raber, J. Apolipoprotein E–low density lipoprotein receptor interaction affects spatial memory retention and brain ApoE levels in an isoform-dependent manner. Neurobiol. Dis., 2014, 64, 150-162.
Raber, J.; Huang, Y.; Ashford, J.W. ApoE genotype accounts for the vast majority of AD risk and AD pathology. Neurobiol. Aging, 2004, 25(5), 641-650.
Strittmatter, W.J.; Saunders, A.M.; Schmechel, D.; Pericak-Vance, M.; Enghild, J.; Salvesen, G.S.; Roses, A. D. Apolipoprotein E: High-avidity binding to beta-amyloid and increased frequency of type 4 allele in late-onset familial Alzheimer disease. Proc. Nat. Acad. Sci., 1993, 90(5), 1977-1981.
Roses, A.D. Apolipoprotein E and Alzheimer's disease: The tip of the susceptibility iceberg. Ann. N. Y. Acad. Sci., 1998, 855(1), 738-743.
van der Flier, W.M.; Pijnenburg, Y.A.; Fox, N.C.; Scheltens, P. Early-onset versus late-onset Alzheimer's disease: the case of the missing APOE ɛ4 allele. The Lancet Neurol., 2011, 10(3), 280-288.
Dong, L.-M.; Wilson, C.; Wardell, M. R.; Simmons, T.; Mahley, R. W.; Weisgraber, K.H.; Agard, D.A. Human apolipoprotein E. Role of arginine 61 in mediating the lipoprotein preferences of the E3 and E4 isoforms. J. Biol. Chem., 1994, 269(35), 22358-22365.
Tanzi, R.E.; Bertram, L. Twenty years of the Alzheimer’s disease amyloid hypothesis: A genetic perspective. Cell, 2005, 120(4), 545-555.
Risner, M.; Saunders, A.; Altman, J.; Ormandy, G.; Craft, S.; Foley, I.; Zvartau-Hind, M.; Hosford, D.; Roses, A., Efficacy of rosiglitazone in a genetically defined population with mild-tomoderate Alzheimer's disease. The Pharmaco. J., 2006, 6(4), 246.
Roses, A.D.; Saunders, A.M., Perspective on a pathogenesis and treatment of Alzheimer’s disease. Alzheimers Dement., 2006, 2(2), 59-70.
Kalita, P.; Sarma, R.; Parida, P.; Kiranmai, C.; Barthakur, M.; Reddy, P. V. B. in silico modelling and structural characterization of γ-aminobutyrate aminotransferase (GABA-AT). Indo Am. J. Pharma. Res., 2014, 4(10), 5066-5073.
Stahl, M.; Guba, W.; Kansy, M. Integrating molecular design resources within modern drug discovery research: The Roche experience. Drug Dis. Today, 2006, 11(7-8), 326-333.
Conway, E.L. A review of the randomized controlled trials of tacrine in the treatment of Alzheimer's disease: Methodologic considerations. Clin. Neuropharm., 1998, 21(1), 8-17.
Goyal, M.; Grover, S.; Dhanjal, J.K.; Goyal, S.; Tyagi, C.; Chacko, S.; Grover, A. Novel natural structure corrector of ApoE4 for checking Alzheimer’s disease: Benefits from high throughput screening and molecular dynamics simulations. BioMed Res. Int. 2013, 2013, http://dx.doi.org/10.1155/2013/620793.
Mayeux, R.; Sano, M., Treatment of Alzheimer's disease. New Eng. J. Med., 1999, 341(22), 1670-1679.
Weisgraber, K.H. Apolipoprotein E: Structure-function relationships. In Advances in protein chemistry, Elsevier: 1994; Vol. 45, pp 249-302.
Calcul, L.; Zhang, B.; Jinwal, U.K.; Dickey, C.A.; Baker, B.J. Natural products as a rich source of tau-targeting drugs for Alzheimer’s disease. Fut. Med. Chem., 2012, 4(13), 1751-1761.
Burley, S.K.; Berman, H.M.; Christie, C.; Duarte, J.M.; Feng, Z.; Westbrook, J.; Young, J.; Zardecki, C. RCSB Protein Data Bank: Sustaining a living digital data resource that enables breakthroughs in scientific research and biomedical education. Protein Sci., 2018, 27(1), 316-330.
Lovell, S.C.; Davis, I.W.; Arendall, W.B.; De Bakker, P.I.; Word, J.M.; Prisant, M.G.; Richardson, J.S.; Richardson, D.C. Structure validation by Cαgeometry: φ, ψand Cβdeviation. Proteins: Structure, Function, and Bioinformatics, 2003, 50(3), 437-450.
Li, C.; Gotz, J. Tau-based therapies in neurodegeneration: opportunities and challenges. Nature reviews. Drug Dis., 2017, 16(12), 863-883.
Kim, S.; Thiessen, P.A.; Bolton, E.E.; Chen, J.; Fu, G.; Gindulyte, A.; Han, L.; He, J.; He, S.; Shoemaker, B.A. PubChem substance and compound databases. Nucleic Acids Res., 2015, 44(D1), D1202-D1213.
Trott, O.; Olson, A.J. AutoDockVina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J. Comp. Chem., 2010, 31(2), 455-461.
Cheng, F.; Li, W.; Zhou, Y.; Shen, J.; Wu, Z.; Liu, G.; Lee, P. W.; Tang, Y. admetSAR: A comprehensive source and free tool for assessment of chemical ADMET properties. ACS Publications: 2012.
Gopalakrishnan, K.; Sowmiya, G.; Sheik, S.; Sekar, K. Ramachandran plot on the web (2.0). Protein Peptide Lett., 2007, 14(7), 669-671.
Desiraju, G.R.; Steiner, T. The weak hydrogen bond: in structural chemistry and biology. International Union of Crystal: 2001; Vol. 9.
Panigrahi, S.K.; Desiraju, G.R. Strong and weak hydrogen bonds in the protein–ligand interface. Proteins: Structure, Function, and Bioinformatics, 2007, 67(1), 128-141.
Ahmed, R.; VanSchouwen, B.; Jafari, N.; Ni, X.; Ortega, J.; Melacini, G. Molecular Mechanism for the (−)-Epigallocatechin Gallate-Induced Toxic to Nontoxic Remodeling of AβOligomers. J. Am. Chem. Soc., 2017, 139(39), 13720-13734.
Jia, J.-J.; Zeng, X.-S.; Song, X.-Q.; Zhang, P.-P.; Chen, L. Diabetes Mellitus and Alzheimer’s Disease: The Protection of Epigallocatechin-3-gallate in Streptozotocin Injection-Induced Models. Frontiers in Pharmacol., 2017, 8, 834.
Cascella, M.; Bimonte, S.; Muzio, M.R.; Schiavone, V.; Cuomo, A. The efficacy of Epigallocatechin-3-gallate (green tea) in the treatment of Alzheimer's disease: An overview of pre-clinical studies and translational perspectives in clinical practice. Infect. Agents Cancer, 2017, 12, 36.
Mandel, S.A.; Amit, T.; Kalfon, L.; Reznichenko, L.; Weinreb, O.; Youdim, M.B. Cell signaling pathways and iron chelation in the neurorestorative activity of green tea polyphenols: special reference to epigallocatechin gallate (EGCG). J. Alzheimer's Dis: JAD 2008, 15(2), 211-22.
Biasibetti, R.; Tramontina, A.C.; Costa, A.P.; Dutra, M.F.; Quincozes-Santos, A.; Nardin, P.; Bernardi, C.L.; Wartchow, K. M.; Lunardi, P.S.; Goncalves, C.A. Green tea (-)epigallocatechin-3-gallate reverses oxidative stress and reduces acetylcholinesterase activity in a streptozotocin-induced model of dementia. Behavioural Brain Res., 2013, 236(1), 186-193.
Rezai-Zadeh, K.; Arendash, G.W.; Hou, H.; Fernandez, F.; Jensen, M.; Runfeldt, M.; Shytle, R.D.; Tan, J. Green tea epigallocatechin-3-gallate (EGCG) reduces beta-amyloid mediated cognitive impairment and modulates tau pathology in Alzheimer transgenic mice. Brain Res., 2008, 1214, 177-187.
Rezai-Zadeh, K.; Shytle, D.; Sun, N.; Mori, T.; Hou, H.; Jeanniton, D.; Ehrhart, J.; Townsend, K.; Zeng, J.; Morgan, D.; Hardy, J.; Town, T.; Tan, J. Green tea epigallocatechin-3-gallate (EGCG) modulates amyloid precursor protein cleavage and reduces cerebral amyloidosis in Alzheimer transgenic mice. J. Neurosci., 2005, 25(38), 8807-8814.
Shen, J.; Cheng, F.; Xu,Y.; Li, W.; Tang, Y. Estimation of ADME properties with substructure pattern recognition. J. Chem. Inf. Mod., 2010, 50(6), 1034-1041.
Szklarczyk, D.; Franceschini, A.; Kuhn, M.; Simonovic, M.; Roth, A.; Minguez, P.; Doerks, T.; Stark, M.; Muller, J.; Bork, P. The STRING database in 201 Impactos de la pandemia COVID-19 y el ASPO en su configuración territorial, Pampa, Revista Interuniversitaria de Estudios Territoriales, Pampa, 2021, núm. 24. DOI: https://doi.org/10.14409/pampa.2021.24.c0040pleo durante la pandemia COVID-19 y el impacto en diferentes sectores económicos del Ecuador, Universidad Tecnológica Indoamérica –Ecuador, V 6-N3, pp1: functional interaction networks of proteins, globally integrated and scored. Nucleic Acids Res.,2010,39(suppl_1), D561-D568.
Publicado
Versiones
- 2025-02-24 (3)
- 2025-02-19 (2)
- 2023-12-30 (1)
