Molecular Modeling Insights on the Pharmaceuticals and Hypotheses of Alzheimer's Disease
Jazyk angličtina Země Spojené arabské emiráty Médium print
Typ dokumentu časopisecké články, přehledy
Grantová podpora
371610/2023-0, 305381/2022-9, 150744/2022-6
Conselho Nacional de Desenvolvimento Científico e Tecnológico - Brazil (CNPq)
0038/21, 0288/22
Financiadora de Estudos e Projetos - Brazil (FINEP)
2024/01071-3
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
PubMed
39238388
DOI
10.2174/0109298673318143240823064403
PII: CMC-EPUB-142820
Knihovny.cz E-zdroje
- Klíčová slova
- AD-related hypotheses, Alzheimer’s disease, amyloid-beta, computational approaches., neuroinflammation, tau protein,
- MeSH
- Alzheimerova nemoc * farmakoterapie metabolismus diagnóza MeSH
- cholinesterasové inhibitory * chemie terapeutické užití farmakologie MeSH
- lidé MeSH
- molekulární modely MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- cholinesterasové inhibitory * MeSH
Alzheimer's disease (AD) stands as the predominant contributor to dementia cases. The ongoing developments in our understanding of its pathogenesis have sparked the interest of researchers, driving them to explore innovative treatment approaches. Existing therapies incorporating cholinesterase inhibitors and/or NMDA antagonists have shown limited improvement in alleviating symptoms. This, in turn, highlights the urgency for the pursuit of more effective therapeutic options. Given the annual rise in the number of individuals affected by dementia, it is imperative to allocate resources and efforts towards the exploration of novel therapeutic options. This review aims to provide a comprehensive overview of the AD-related hypotheses, along with the computational approaches employed in research within each hypothesis. In this comprehensive review, the authors shed light on using various computational tools, including diverse case studies, in the pursuit of finding efficacious treatments for AD. The development of more sophisticated diagnostic techniques is crucial, enabling early detection and intervention in the battle against this challenging condition. The potential treatments investigated in this analysis are poised to assume ever more significant functions in both preventing and treating AD, ultimately enhancing the management of the condition and the overall well-being of individuals affected by AD.
Center for Natural and Human Sciences Federal University of ABC Santo André 09280 560 Brazil
Department of Chemistry Federal University of Lavras Lavras 37200 000 Brazil
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Knopman D.S.; Amieva H.; Petersen R.C.; Chételat G.; Holtzman D.M.; Hyman B.T.; Nixon R.A.; Jones D.T.; Alzheimer disease. Nat Rev Dis Primers 2021,7(1),33 PubMed DOI
DeTure M.A.; Dickson D.W.; The neuropathological diagnosis of Alzheimer’s disease. Mol Neurodegener 2019,14(1),32 PubMed DOI
de Castro A.A.; Soares F.V.; Pereira A.F.; Polisel D.A.; Caetano M.S.; Leal D.H.S.; da Cunha E.F.F.; Nepovimova E.; Kuca K.; Ramalho T.C.; Non-conventional compounds with potential therapeutic effects against Alzheimer’s disease. Expert Rev Neurother 2019,19(5),375-395 PubMed DOI
Chen Z.R.; Huang J.B.; Yang S.L.; Hong F.F.; Role of cholinergic signaling in Alzheimer’s disease. Molecules 2022,27(6),1816 PubMed DOI
Scheltens P.; De Strooper B.; Kivipelto M.; Holstege H.; Chételat G.; Teunissen C.E.; Cummings J.; van der Flier W.M.; Alzheimer’s disease. Lancet 2021,397(10284),1577-1590 PubMed DOI
Yiannopoulou K.G.; Papageorgiou S.G.; Current and future treatments in alzheimer disease: An update. J Cent Nerv Syst Dis 2020,12 PubMed DOI
Tatulian S.A.; Challenges and hopes for Alzheimer’s disease. Drug Discov Today 2022,27(4),1027-1043 PubMed DOI
Dubois B.; Hampel H.; Feldman H.H.; Scheltens P.; Aisen P.; Andrieu S.; Bakardjian H.; Benali H.; Bertram L.; Blennow K.; Broich K.; Cavedo E.; Crutch S.; Dartigues J.F.; Duyckaerts C.; Epelbaum S.; Frisoni G.B.; Gauthier S.; Genthon R.; Gouw A.A.; Habert M.O.; Holtzman D.M.; Kivipelto M.; Lista S.; Molinuevo J.L.; O’Bryant S.E.; Rabinovici G.D.; Rowe C.; Salloway S.; Schneider L.S.; Sperling R.; Teichmann M.; Carrillo M.C.; Cummings J.; Jack C.R.; Proceedings of the meeting of the international working group (IWG) and the American alzheimer’s association on “the preclinical state of AD”; July 23, 2015; wshington DC, USA. preclinical alzheimer’s disease: Definition, natural history, and diagnostic criteria. Alzheimers Dement 2016,12(3),292-323 PubMed DOI
Alzheimer’s disease facts and figures. Alzheimers Dement 2021,17(3),327-406 PubMed DOI
Heneka M.T.; Carson M.J.; Khoury J.E.; Landreth G.E.; Brosseron F.; Feinstein D.L.; Jacobs A.H.; Wyss-Coray T.; Vitorica J.; Ransohoff R.M.; Herrup K.; Frautschy S.A.; Finsen B.; Brown G.C.; Verkhratsky A.; Yamanaka K.; Koistinaho J.; Latz E.; Halle A.; Petzold G.C.; Town T.; Morgan D.; Shinohara M.L.; Perry V.H.; Holmes C.; Bazan N.G.; Brooks D.J.; Hunot S.; Joseph B.; Deigendesch N.; Garaschuk O.; Boddeke E.; Dinarello C.A.; Breitner J.C.; Cole G.M.; Golenbock D.T.; Kummer M.P.; Neuroinflammation in Alzheimer’s disease. Lancet Neurol 2015,14(4),388-405 PubMed DOI
Li H.M.; Yu S.P.; Fan T.Y.; Zhong Y.; Gu T.; Wu W.Y.; Zhao C.; Chen Z.; Chen M.; Li N.G.; Wang X.L.; Design, synthesis, and biological activity evaluation of BACE1 inhibitors with antioxidant activity. Drug Dev Res 2020,81(2),206-214 PubMed DOI
Nascimento I.J.S.; de Aquino T.M.; da Silva-Júnior E.F.; The new era of drug discovery: The power of computer-aided drug design (CADD). Lett Drug Des Discov 2022,19(11),951-955 DOI
Terstappen G.C.; Reggiani A.; In silico research in drug discovery. Trends Pharmacol Sci 2001,22(1),23-26 PubMed DOI
Lonsdale R.; Ranaghan K.E.; Mulholland A.J.; Computational enzymology. Chem Commun 2010,46(14),2354-2372 PubMed DOI
Nemukhin A.V.; Grigorenko B.L.; Lushchekina S.V.; Varfolomeev S.D.; Quantum chemical modelling in the research of molecular mechanisms of enzymatic catalysis. Russ Chem Rev 2012,81(11),1011-1025 DOI
Ramalho T.C.; de Castro A.A.; Leal D.H.S.; Teixeira J.P.; da Cunha E.F.F.; Kuca K.; Assessing the therapeutic and toxicological profile of novel acetylcholinesterase reactivators: Value of in silico and in vitro Data. Curr Med Chem 2023,30(36),4149-4166 PubMed DOI
Oliveira S.S.C.; Correia C.A.; Santos V.S.; da Cunha E.F.F.; de Castro A.A.; Ramalho T.C.; Devereux M.; McCann M.; Branquinha M.H.; Santos A.L.S.; Silver(I) and copper(ii) 1,10-phenanthroline-5,6-dione complexes as promising antivirulence strategy against leishmania: Focus on Gp63 (Leishmanolysin). Trop Med Infect Dis 2023,8(7),348 PubMed DOI
Kuca K.; Musilek K.; Jun D.; Nepovimova E.; Soukup O.; Korabecny J.; França T.C.C.; de Castro A.A.; Krejcar O.; da Cunha E.F.F.; Ramalho T.C.; Oxime K074 – in vitro and in silico reactivation of acetylcholinesterase inhibited by nerve agents and pesticides. Toxin Rev 2020,39(2),157-166 DOI
Assis L.C.; de Castro A.A.; de Jesus J.P.A.; da Cunha E.F.F.; Nepovimova E.; Krejcar O.; Kuca K.; Ramalho T.C.; La Porta F.A.; Theoretical insights into the effect of halogenated substituent on the electronic structure and spectroscopic properties of the favipiravir tautomeric forms and its implications for the treatment of COVID-19. RSC Adv 2021,11(56),35228-35244 PubMed DOI
de Jesus J.P.A.; Assis L.C.; de Castro A.A.; da Cunha E.F.F.; Nepovimova E.; Kuca K.; de Castro Ramalho T.; de Almeida La Porta F.; Effect of drug metabolism in the treatment of SARS-CoV-2 from an entirely computational perspective. Sci Rep 2021,11(1),19998 PubMed DOI
de Castro A.A.; Assis L.C.; da Cunha E.F.F.; Ramalho T.C.; La Porta F.A.; New in silico insights into the application of (hydroxy)chloroquine with macrolide antibiotic co-crystals against the SARS-CoV-2 virus. 2022,2
da Silva A.P.; de Angelo R.M.; de Paula H.; Honório K.M.; da Silva A.B.F.; Drug design of new 5-HT6 antagonists: A QSAR study of arylsulfonamide derivatives. Struct Chem 2020,31(4),1585-1597 DOI
Chiari L.P.A.; da Silva A.P.; de Oliveira A.A.; Lipinski C.F.; Honório K.M.; da Silva A.B.F.; Drug design of new sigma-1 antagonists against neuropathic pain: A QSAR study using partial least squares and artificial neural networks. J Mol Struct 2021,1223,129156 DOI
Pantaleao S.Q.; Fujii D.G.V.; Maltarollo V.G.; da C Silva D.; Trossini G.H.G.; Weber K.C.; Scott L.P.B.; Honorio K.M.; The role of QSAR and virtual screening studies in type 2 diabetes drug discovery. Med Chem 2017,13(8),706-720 PubMed
de Castro A.A.; Caetano M.S.; Silva T.C.; Mancini D.T.; Rocha E.P.; da Cunha E.F.F.; Ramalho T.C.; Molecular docking, metal substitution and hydrolysis reaction of chiral substrates of phosphotriesterase. Comb Chem High Throughput Screen 2016,19(4),334-344 PubMed DOI
Castro A.A.; de ; Prandi I.G.; Kuca K.; Ramalho T.C.; Organophosphate-degrading enzymes: Molecular basis and perspectives for enzymatic bioremediation of agrochemicals. Agrotechnical Sci 2017,41,471-482 DOI
de Castro A.A.; Assis L.C.; Silva D.R.; Corrêa S.; Assis T.M.; Gajo G.C.; Soares F.V.; Ramalho T.C.; Computational enzymology for degradation of chemical warfare agents: promising technologies for remediation processes. AIMS Microbiol 2017,3(1),108-135 PubMed DOI
Soares F.V.; De Castro A.A.; Pereira A.F.; Leal D.H.S.; Mancini D.T.; Krejcar O.; Ramalho T.C.; Da Cunha E.F.F.; Kuca K.; Theoretical studies applied to the evaluation of the DFPase bioremediation potential against chemical warfare agents intoxication. Int J Mol Sci 2018,19(4),1257 PubMed DOI
Pereira A.F.; de Castro A.A.; Soares F.V.; Soares Leal D.H.; da Cunha E.F.F.; Mancini D.T.; Ramalho T.C.; Development of technologies applied to the biodegradation of warfare nerve agents: Theoretical evidence for asymmetric homogeneous catalysis. Chem Biol Interact 2019,308,323-331 PubMed DOI
Polisel D.A.; de Castro A.A.; Mancini D.T.; da Cunha E.F.F.; França T.C.C.; Ramalho T.C.; Kuca K.; Slight difference in the isomeric oximes K206 and K203 makes huge difference for the reactivation of organophosphorus-inhibited AChE: Theoretical and experimental aspects. Chem Biol Interact 2019,309,108671 PubMed DOI
de Castro A.A.; Soares F.V.; Pereira A.F.; Silva T.C.; Silva D.R.; Mancini D.T.; Caetano M.S.; da Cunha E.F.F.; Ramalho T.C.; Asymmetric biodegradation of the nerve agents Sarin and VX by human dUTPase: Chemometrics, molecular docking and hybrid QM/MM calculations. J Biomol Struct Dyn 2019,37(8),2154-2164 PubMed DOI
van der Kamp M.W.; Mulholland A.J.; Combined quantum mechanics/molecular mechanics (QM/MM) methods in computational enzymology. Biochemistry 2013,52(16),2708-2728 PubMed DOI
Sharma H.; Raju B.; Narendra G.; Motiwale M.; Sharma B.; Verma H.; Silakari O.; QM/MM studies on enzyme catalysis and insight into designing of new inhibitors by ONIOM approach: Recent update. ChemistrySelect 2023,8(1),e202203319 DOI
Huang S.Y.; Zou X.; Advances and challenges in protein-ligand docking. Int J Mol Sci 2010,11(8),3016-3034 PubMed DOI
Jones G.; Willett P.; Glen R.C.; Leach A.R.; Taylor R.; Development and validation of a genetic algorithm for flexible docking. J Mol Biol 1997,267(3),727-748 PubMed DOI
Goodsell D.S.; Olson A.J.; Automated docking of substrates to proteins by simulated annealing. Proteins 1990,8(3),195-202 PubMed DOI
Goodsell D.S.; Morris G.M.; Olson A.J.; Automated docking of flexible ligands: Applications of autodock. J Mol Recognit 1996,9(1),1-5 PubMed DOI
Rarey M.; Kramer B.; Lengauer T.; Klebe G.; A fast flexible docking method using an incremental construction algorithm. J Mol Biol 1996,261(3),470-489 PubMed DOI
Thomsen R.; Christensen M.H.; MolDock: A new technique for high-accuracy molecular docking. J Med Chem 2006,49(11),3315-3321 PubMed DOI
Kitchen D.B.; Decornez H.; Furr J.R.; Bajorath J.; Docking and scoring in virtual screening for drug discovery: Methods and applications. Nat Rev Drug Discov 2004,3(11),935-949 PubMed DOI
Hollingsworth, S.A.; Dror, R.O. Molecular dynamics simulation for all. Neuron 2018,99(6),1129-1143 PubMed DOI
Durrant J.D.; McCammon J.A.; Molecular dynamics simulations and drug discovery. BMC Biol 2011,9(1),71 PubMed DOI
Vidal-Limon A.; Aguilar-Toalá J.E.; Liceaga A.M.; Integration of molecular docking analysis and molecular dynamics simulations for studying food proteins and bioactive peptides. J Agric Food Chem 2022,70(4),934-943 PubMed DOI
Filipe H.A.L.; Loura L.M.S.; Molecular dynamics simulations: Advances and applications. Molecules 2022,27(7),2105 PubMed DOI
Wu X.; Xu L.Y.; Li E.M.; Dong G.; Application of molecular dynamics simulation in biomedicine. Chem Biol Drug Des 2022,99(5),789-800 PubMed DOI
Fu H.; Chen H.; Blazhynska M.; Goulard Coderc de Lacam E.; Szczepaniak F.; Pavlova A.; Shao X.; Gumbart J.C.; Dehez F.; Roux B.; Cai W.; Chipot C.; Accurate determination of protein:ligand standard binding free energies from molecular dynamics simulations. Nat Protoc 2022,17(4),1114-1141 PubMed DOI
Wang M.; Incecik A.; Yang C.; Gupta M.K.; Królczyk G.; Andriukaitis D.; Li Z.; A critical review on molecular dynamics applied to structure fracture and failure analysis. Eng Anal Bound Elem 2023,150,413-422 DOI
Guimarães A.P.; Ramalho T.C.; França T.C.C.; Preventing the return of smallpox: Molecular modeling studies on thymidylate kinase from Variola virus. J Biomol Struct Dyn 2014,32(10),1601-1612 PubMed DOI
Karplus M.; McCammon J.A.; Molecular dynamics simulations of biomolecules. Nat Struct Biol 2002,9(9),646-652 PubMed DOI
Alonso H.; Bliznyuk A.A.; Gready J.E.; Combining docking and molecular dynamic simulations in drug design. Med Res Rev 2006,26(5),531-568 PubMed DOI
Weiner P.K.; Kollman P.A.; : Assisted model building with energy refinement. A general program for modeling molecules and their interactions. J Comput Chem 1981,2(3),287-303 DOI
Brooks B.R.; Bruccoleri R.E.; Olafson B.D.; States D.J.; Swaminathan S.; Karplus M.; : A program for macromolecular energy, minimization, and dynamics calculations. J Comput Chem 1983,4(2),187-217 DOI
Kalé L.; Skeel R.; Bhandarkar M.; Brunner R.; Gursoy A.; Krawetz N.; Phillips J.; Shinozaki A.; Varadarajan K.; Schulten K.; NAMD2: Greater scalability for parallel molecular dynamics. J Comput Phys 1999,151(1),283-312 DOI
Phillips J.C.; Braun R.; Wang W.; Gumbart J.; Tajkhorshid E.; Villa E.; Chipot C.; Skeel R.D.; Kalé L.; Schulten K.; Scalable molecular dynamics with NAMD. J Comput Chem 2005,26(16),1781-1802 PubMed DOI
Scott W.R.P.; Hünenberger P.H.; Tironi I.G.; Mark A.E.; Billeter S.R.; Fennen J.; Torda A.E.; Huber T.; Krüger P.; van Gunsteren W.F.; The GROMOS biomolecular simulation program package. J Phys Chem A 1999,103(19),3596-3607 DOI
Ramalho T.C.; de Castro A.A.; Silva D.R.; Silva M.C.; Franca T.C.C.; Bennion B.J.; Kuca K.; Computational enzymology and organophosphorus degrading enzymes: Promising approaches toward remediation technologies of warfare agents and pesticides. Curr Med Chem 2016,23(10),1041-1061 PubMed DOI
Jorgensen W.L.; Foundations of biomolecular modeling. Cell 2013,155(6),1199-1202 PubMed DOI
da Silva Gonçalves A.; França T.C.C.; Caetano M.S.; Ramalho T.C.; Reactivation steps by 2-PAM of tabun-inhibited human acetylcholinesterase: Reducing the computational cost in hybrid QM/MM methods. J Biomol Struct Dyn 2014,32(2),301-307 PubMed DOI
Brunk E.; Rothlisberger U.; Mixed quantum mechanical/molecular mechanical molecular dynamics simulations of biological systems in ground and electronically excited states. Chem Rev 2015,115(12),6217-6263 PubMed DOI
Warshel A.; Levitt M.; Theoretical studies of enzymic reactions: Dielectric, electrostatic and steric stabilization of the carbonium ion in the reaction of lysozyme. J Mol Biol 1976,103(2),227-249 PubMed DOI
Malaspina T.; Coutinho K.; Canuto S.; Ab initio calculation of hydrogen bonds in liquids: A sequential Monte Carlo quantum mechanics study of pyridine in water. J Chem Phys 2002,117(4),1692-1699 DOI
Abdolmaleki A.; Ghasemi F.; Ghasemi J.B.; Computer-aided drug design to explore cyclodextrin therapeutics and biomedical applications. Chem Biol Drug Des 2017,89(2),257-268 PubMed DOI
Giordano D.; Biancaniello C.; Argenio M.A.; Facchiano A.; Drug design by pharmacophore and virtual screening approach. Pharmaceuticals 2022,15(5),646 PubMed DOI
Jiang Y.; Gao H.; Pharmacophore-based drug design for potential AChE inhibitors from traditional chinese medicine database. Bioorg Chem 2018,76,400-414 PubMed DOI
Maia E.H.B.; Assis L.C.; de Oliveira T.A.; da Silva A.M.; Taranto A.G.; Structure-based virtual screening: from classical to artificial intelligence. Front Chem 2020,8,343 PubMed DOI
Lionta E.; Spyrou G.; Vassilatis D.; Cournia Z.; Structure-based virtual screening for drug discovery: Principles, applications and recent advances. Curr Top Med Chem 2014,14(16),1923-1938 PubMed DOI
Ittner L.M.; Ke Y.D.; Delerue F.; Bi M.; Gladbach A.; van Eersel J.; Wölfing H.; Chieng B.C.; Christie M.J.; Napier I.A.; Eckert A.; Staufenbiel M.; Hardeman E.; Götz J.; Dendritic function of tau mediates amyloid-beta toxicity in Alzheimer’s disease mouse models. Cell 2010,142(3),387-397 PubMed DOI
Corbett A.; Pickett J.; Burns A.; Corcoran J.; Dunnett S.B.; Edison P.; Hagan J.J.; Holmes C.; Jones E.; Katona C.; Kearns I.; Kehoe P.; Mudher A.; Passmore A.; Shepherd N.; Walsh F.; Ballard C.; Drug repositioning for Alzheimer’s disease. Nat Rev Drug Discov 2012,11(11),833-846 PubMed DOI
Ballard C.; Corbett A.; Sharp S.; Aligning the evidence with practice: NICE guidelines for drug treatment of Alzheimer’s disease. Expert Rev Neurother 2011,11(3),327-329 PubMed DOI
Liu P.P.; Xie Y.; Meng X.Y.; Kang J.S.; History and progress of hypotheses and clinical trials for Alzheimer’s disease. Signal Transduct Target Ther 2019,4(1),29 PubMed DOI
Contestabile A.; The history of the cholinergic hypothesis. Behav Brain Res 2011,221(2),334-340 PubMed DOI
Davies P.; Maloney A.J.; Selective loss of central cholinergic neurons in Alzheimer’s disease. Lancet 1976,308(8000),1403 PubMed DOI
Hörnberg A.; Tunemalm A.K.; Ekström F.; Crystal structures of acetylcholinesterase in complex with organophosphorus compounds suggest that the acyl pocket modulates the aging reaction by precluding the formation of the trigonal bipyramidal transition state. Biochemistry 2007,46(16),4815-4825 PubMed DOI
Bowen D.M.; Smith C.B.; White P.; Davison A.N.; Neurotransmitter-related enzymes and indices of hypoxia in senile dementia and other abiotrophies. Brain 1976,99(3),459-496 PubMed DOI
Kar S.; Issa A.M.; Seto D.; Auld D.S.; Collier B.; Quirion R.; Amyloid beta-peptide inhibits high-affinity choline uptake and acetylcholine release in rat hippocampal slices. J Neurochem 1998,70(5),2179-2187 PubMed DOI
Auld D.S.; Kar S.; Quirion R.; β-Amyloid peptides as direct cholinergic neuromodulators: A missing link? Trends Neurosci 1998,21(1),43-49 PubMed DOI
Nordberg A.; Alafuzoff I.; Winblad B.; Nicotinic and muscarinic subtypes in the human brain: Changes with aging and dementia. J Neurosci Res 1992,31(1),103-111 PubMed DOI
Barage S.H.; Sonawane K.D.; Amyloid cascade hypothesis: Pathogenesis and therapeutic strategies in Alzheimer’s disease. Neuropeptides 2015,52,1-18 PubMed DOI
Franklin M.C.; Rudolph M.J.; Ginter C.; Cassidy M.S.; Cheung J.; Structures of paraoxon-inhibited human acetylcholinesterase reveal perturbations of the acyl loop and the dimer interface. Proteins 2016,84(9),1246-1256 PubMed DOI
Reitz C.; Brayne C.; Mayeux R.; Epidemiology of Alzheimer disease. Nat Rev Neurol 2011,7(3),137-152 PubMed DOI
Lleó A.; Greenberg S.M.; Growdon J.H.; Current pharmacotherapy for Alzheimer’s disease. Annu Rev Med 2006,57(1),513-533 PubMed DOI
Hebert L.E.; Scherr P.A.; Bienias J.L.; Bennett D.A.; Evans D.A.; Alzheimer disease in the US population: prevalence estimates using the 2000 census. Arch Neurol 2003,60(8),1119-1122 PubMed DOI
Doody R.S.; Stevens J.C.; Beck C.; Dubinsky R.M.; Kaye J.A.; Gwyther L.; Mohs R.C.; Thal L.J.; Whitehouse P.J.; DeKosky S.T.; Cummings J.L.; Practice parameter: management of dementia (an evidence-based review). Report of the quality standards subcommittee of the american academy of neurology. Neurology 2001,56(9),1154-1166 PubMed DOI
Giacobini E.; Cholinesterases: new roles in brain function and in Alzheimer’s disease. Neurochem Res 2003,28(3/4),515-522 PubMed DOI
Giacobini E.; Long-term stabilizing effect of cholinesterase inhibitors in the therapy of Alzheimer’ disease. J Neural Transm Suppl 2002,62(62),181-187 PubMed DOI
Rogers S.L.; Farlow M.R.; Doody R.S.; Mohs R.; Friedhoff L.T.; Donepezil Study Group.A 24-week, double-blind, placebo-controlled trial of donepezil in patients with Alzheimer’s disease. Neurology 1998,50(1),136-145 PubMed DOI
Corey-Bloom J.; Anand R.; Veach J.; A randomized trial evaluating the efficacy and safety of ENA 713 (rivastigmine tartrate), a new acetylcholinesterase inhibitor, in patients with mild to moderately severe Alzheimer's disease. Int J Geriatr Psychiatry 1998,1(2),55-65
Tariot P.N.; Solomon P.R.; Morris J.C.; Kershaw P.; Lilienfeld S.; Ding C.; A 5-month, randomized, placebo- controlled trial of galantamine in AD. Neurology 2000,54(12),2269-2276 PubMed DOI
Cummings J.L.; Cholinesterase inhibitors: A new class of psychotropic compounds. Am J Psychiatry 2000,157(1),4-15 PubMed DOI
Ryan J.; Scali J.; Carriere I.; Ritchie K.; Ancelin M.L.; Hormonal treatment, mild cognitive impairment and Alzheimer’s disease. Int Psychogeriatr 2008,20(1),47-56 PubMed DOI
Gauthier S.; Juby A.; Dalziel W.; Réhel B.; Schecter R.; EXPLORE investigators. Effects of rivastigmine on common symptomatology of Alzheimer’s disease (EXPLORE). Curr Med Res Opin 2010,26(5),1149-1160 PubMed DOI
Lockhart I.A.; Mitchell S.A.; Kelly S.; Safety and tolerability of donepezil, rivastigmine and galantamine for patients with Alzheimer’s disease: Systematic review of the ‘real-world’ evidence. Dement Geriatr Cogn Disord 2009,28(5),478-492 PubMed DOI
Holtzman D.M.; Morris J.C.; Goate A.M.; Alzheimer’s disease: The challenge of the second century. Sci Transl Med 2011,3(77),77sr1 PubMed DOI
Giacobini E.; Cholinesterase inhibitors stabilize Alzheimer’s disease. Ann N Y Acad Sci 2000,920(1),321-327 PubMed DOI
Crismon M.L.; Tacrine: First drug approved for Alzheimer’s disease. Ann Pharmacother 1994,28(6),744-751 PubMed DOI
Mehta M.; Adem A.; Sabbagh M.; New acetylcholinesterase inhibitors for Alzheimer’s disease. Int J Alzheimer’s Dis 2012 DOI
Cacabelos R.; Donepezil in Alzheimer’s disease: From conventional trials to pharmacogenetics. Neuropsychiatr Dis Treat 2007,3(3),303-333 PubMed
Birks J.S.; Harvey R.J.; Donepezil for dementia due to Alzheimer’s disease. Cochrane Libr 2018,2018(6),CD001190 PubMed DOI
Ballard C.G.; Advances in the treatment of Alzheimer’s disease: benefits of dual cholinesterase inhibition. Eur Neurol 2002,47(1),64-70 PubMed DOI
Gao H.; Jiang Y.; Zhan J.; Sun Y.; Pharmacophore-based drug design of AChE and BChE dual inhibitors as potential anti-Alzheimer’s disease agents. Bioorg Chem 2021,114,105149 PubMed DOI
Irwin J.J.; Shoichet B.K.; ZINC-a free database of commercially available compounds for virtual screening. J Chem Inf Model 2005,45(1),177-182 PubMed DOI
Jiang Y.; Gao H.; Pharmacophore-based drug design for the identification of novel butyrylcholinesterase inhibitors against Alzheimer’s disease. Phytomedicine 2019,54,278-290 PubMed DOI
Joubert J.; Kapp E.; Discovery of 9-phenylacridinediones as highly selective butyrylcholinesterase inhibitors through structure-based virtual screening. Bioorg Med Chem Lett 2020,30(9),127075 PubMed DOI
Codony S.; Pont C.; Griñán-Ferré C.; Di Pede-Mattatelli A.; Calvó-Tusell C.; Feixas F.; Osuna S.; Jarné-Ferrer J.; Naldi M.; Bartolini M.; Loza M.I.; Brea J.; Pérez B.; Bartra C.; Sanfeliu C.; Juárez-Jiménez J.; Morisseau C.; Hammock B.D.; Pallàs M.; Vázquez S.; Muñoz-Torrero D.; Discovery and in vivo proof of concept of a highly potent dual inhibitor of soluble epoxide hydrolase and acetylcholinesterase for the treatment of Alzheimer’s disease. J Med Chem 2022,65(6),4909-4925 PubMed DOI
Ahmed Ali Abdusalam A.; Vikneswaran M.; Novel acetylcholinesterase inhibitors identified from zinc database using docking-based virtual screening for Alzheimer’s disease. ChemistrySelect 2020,5(12),3593-3599 DOI
Son M.; Park C.; Rampogu S.; Zeb A.; Lee K.W.; Discovery of novel acetylcholinesterase inhibitors as potential candidates for the treatment of Alzheimer’s disease. Int J Mol Sci 2019,20(4),1000 PubMed DOI
Fatiha Muhammad E.; Kumar A.; Wahab H.A.; Zhang K.Y.J.; Identification of 1,2,4-triazolylthioethanone scaffold for the design of new acetylcholinesterase inhibitors. Mol Inform 2021,40(8),2100020 PubMed DOI
Reiss A.B.; Arain H.A.; Stecker M.M.; Siegart N.M.; Kasselman L.J.; Amyloid toxicity in Alzheimer’s disease. Rev Neurosci 2018,29(6),613-627 PubMed DOI
Imbimbo B.P.; Ippati S.; Watling M.; Imbimbo C.; Role of monomeric amyloid-β in cognitive performance in Alzheimer’s disease: Insights from clinical trials with secretase inhibitors and monoclonal antibodies. Pharmacol Res 2023,187,106631 PubMed DOI
Uddin M.S.; Kabir M.T.; Rahman M.S.; Behl T.; Jeandet P.; Ashraf G.M.; Najda A.; Bin-Jumah M.N.; El-Seedi H.R.; Abdel-Daim M.M.; Revisiting the amyloid cascade hypothesis: From anti-aβ therapeutics to auspicious new ways for Alzheimer’s disease. Int J Mol Sci 2020,21(16),5858 PubMed DOI
Chen G.; Xu T.; Yan Y.; Zhou Y.; Jiang Y.; Melcher K.; Xu H.E.; Amyloid beta: Structure, biology and structure-based therapeutic development. Acta Pharmacol Sin 2017,38(9),1205-1235 PubMed DOI
Papadopoulos N.; Suelves N.; Perrin F.; Vadukul D.M.; Vrancx C.; Constantinescu S.N.; Kienlen-Campard P.; Structural determinant of β-amyloid formation: from transmembrane protein dimerization to β-amyloid aggregates. Biomedicines 2022,10(11),2753 PubMed DOI
Hampel H.; Hardy J.; Blennow K.; Chen C.; Perry G.; Kim S.H.; Villemagne V.L.; Aisen P.; Vendruscolo M.; Iwatsubo T.; Masters C.L.; Cho M.; Lannfelt L.; Cummings J.L.; Vergallo A.; The amyloid-β pathway in Alzheimer’s disease. Mol Psychiatry 2021,26(10),5481-5503 PubMed DOI
Gulisano W.; Maugeri D.; Baltrons M.A.; Fà M.; Amato A.; Palmeri A.; D’Adamio L.; Grassi C.; Devanand D.P.; Honig L.S.; Puzzo D.; Arancio O.; Role of amyloid-β and tau proteins in Alzheimer’s disease: Confuting the amyloid cascade. J Alzheimers Dis 2018,64(s1),S611-S631 PubMed DOI
Shaker B.; Ahmad S.; Lee J.; Jung C.; Na D.; In silico methods and tools for drug discovery. Comput Biol Med 2021,137,104851 PubMed DOI
Youn K.; Park J.H.; Lee S.; Lee S.; Lee J.; Yun E.Y.; Jeong W.S.; Jun M.; BACE1 inhibition by genistein: Biological evaluation, kinetic analysis, and molecular docking simulation. J Med Food 2018,21(4),416-420 PubMed DOI
Egan M.F.; Kost J.; Voss T.; Mukai Y.; Aisen P.S.; Cummings J.L.; Tariot P.N.; Vellas B.; van Dyck C.H.; Boada M.; Zhang Y.; Li W.; Furtek C.; Mahoney E.; Harper Mozley L.; Mo Y.; Sur C.; Michelson D.; Randomized trial of verubecestat for prodromal Alzheimer’s disease. N Engl J Med 2019,380(15),1408-1420 PubMed DOI
Saravanan K.; Sivanandam M.; Hunday G.; Mathiyalagan L.; Kumaradhas P.; Investigation of intermolecular interactions and stability of verubecestat in the active site of BACE1: Development of first model from QM/MM-based charge density and MD analysis. J Biomol Struct Dyn 2019,37(9),2339-2354 PubMed DOI
Ali M.A.; Vuree S.; Goud H.; Hussain T.; Nayarisseri A.; Singh S.K.; Identification of high-affinity small molecules targeting gamma secretase for the treatment of Alzheimer’s disease. Curr Top Med Chem 2019,19(13),1173-1187 PubMed DOI
Jabir N.R.; Rehman M.T.; Alsolami K.; Shakil S.; Zughaibi T.A.; Alserihi R.F.; Khan M.S.; AlAjmi M.F.; Tabrez S.; Concatenation of molecular docking and molecular simulation of BACE-1, γ-secretase targeted ligands: In pursuit of Alzheimer’s treatment. Ann Med 2021,53(1),2332-2344 PubMed DOI
Jabir N.R.; Shakil S.; Tabrez S.; Khan M.S.; Rehman M.T.; Ahmed B.A.; In silico screening of glycogen synthase kinase-3β targeted ligands against acetylcholinesterase and its probable relevance to Alzheimer’s disease. J Biomol Struct Dyn 2021,39(14),5083-5092 PubMed DOI
Jabir N.R.; Rehman M.T.; Tabrez S.; Alserihi R.F.; AlAjmi M.F.; Khan M.S.; Husain F.M.; Ahmed B.A.; Identification of butyrylcholinesterase and monoamine oxidase B targeted ligands and their putative application in Alzheimer’s treatment: A computational strategy. Curr Pharm Des 2021,27(20),2425-2434 PubMed DOI
Chawla P.A.; >In Silico design and evaluation of triazine based 4-thiazolidinone (tbt) analogues as anti Alzheimer’s agents through bace 1 inhibition. Biomed J Sci Tech Res 2022,46(3),37433-37441 DOI
Frost B.; Jacks R.L.; Diamond M.I.; Propagation of tau misfolding from the outside to the inside of a cell. J Biol Chem 2009,284(19),12845-12852 PubMed DOI
Medeiros R.; Baglietto-Vargas D.; LaFerla F.M.; The role of tau in Alzheimer’s disease and related disorders. CNS Neurosci Ther 2011,17(5),514-524 PubMed DOI
Braak H.; Braak E.; Neuropathological stageing of Alzheimer-related changes. Acta Neuropathol 1991,82(4),239-259 PubMed DOI
Hutton M.; Lendon C.L.; Rizzu P.; Baker M.; Froelich S.; Houlden H.; Pickering-Brown S.; Chakraverty S.; Isaacs A.; Grover A.; Hackett J.; Adamson J.; Lincoln S.; Dickson D.; Davies P.; Petersen R.C.; Stevens M.; de Graaff E.; Wauters E.; van Baren J.; Hillebrand M.; Joosse M.; Kwon J.M.; Nowotny P.; Che L.K.; Norton J.; Morris J.C.; Reed L.A.; Trojanowski J.; Basun H.; Lannfelt L.; Neystat M.; Fahn S.; Dark F.; Tannenberg T.; Dodd P.R.; Hayward N.; Kwok J.B.J.; Schofield P.R.; Andreadis A.; Snowden J.; Craufurd D.; Neary D.; Owen F.; Oostra B.A.; Hardy J.; Goate A.; van Swieten J.; Mann D.; Lynch T.; Heutink P.; Association of missense and 5′-splice-site mutations in tau with the inherited dementia FTDP-17. Nature 1998,393(6686),702-705 PubMed DOI
SantaCruz K.; Lewis J.; Spires T.; Paulson J.; Kotilinek L.; Ingelsson M.; Guimaraes A.; DeTure M.; Ramsden M.; McGowan E.; Forster C.; Yue M.; Orne J.; Janus C.; Mariash A.; Kuskowski M.; Hyman B.; Hutton M.; Ashe K.H.; Tau suppression in a neurodegenerative mouse model improves memory function. Science 2005,309(5733),476-481 PubMed DOI
Clavaguera F.; Bolmont T.; Crowther R.A.; Abramowski D.; Frank S.; Probst A.; Fraser G.; Stalder A.K.; Beibel M.; Staufenbiel M.; Jucker M.; Goedert M.; Tolnay M.; Transmission and spreading of tauopathy in transgenic mouse brain. Nat Cell Biol 2009,11(7),909-913 PubMed DOI
Ballatore C.; Lee V.M.Y.; Trojanowski J.Q.; Tau-mediated neurodegeneration in Alzheimer’s disease and related disorders. Nat Rev Neurosci 2007,8(9),663-672 PubMed DOI
Bakota L.; Brandt R.; Tau biology and tau-directed therapies for Alzheimer’s disease. Drugs 2016,76(3),301-313 PubMed DOI
Pradeepkiran J.A.; Reddy P.H.; Structure based design and molecular docking studies for phosphorylated tau inhibitors in Alzheimer’s disease. Cells 2019,8(3),260 PubMed DOI
Pradeepkiran J.A.; Munikumar M.; Reddy A.P.; Reddy P.H.; Protective effects of a small molecule inhibitor ligand against hyperphosphorylated tau-induced mitochondrial and synaptic toxicities in Alzheimer disease. Hum Mol Genet 2021,31(2),244-261 PubMed DOI
Vilar S.; Cozza G.; Moro S.; Medicinal chemistry and the molecular operating environment (MOE): Application of QSAR and molecular docking to drug discovery. Curr Top Med Chem 2008,8(18),1555-1572 PubMed DOI
Schmidtke P.; Le Guilloux V.; Maupetit J.; Tufféry P.; fpocket: Online tools for protein ensemble pocket detection and tracking. Nucleic Acids Res 2010,38(Web Server),W582-W589 PubMed DOI
Shukla R.; Singh T.R.; Virtual screening, pharmacokinetics, molecular dynamics and binding free energy analysis for small natural molecules against cyclin-dependent kinase 5 for Alzheimer’s disease. J Biomol Struct Dyn 2020,38(1),248-262 PubMed DOI
Trudler D.; Farfara D.; Frenkel D.; Toll-like receptors expression and signaling in glia cells in neuro-amyloidogenic diseases: Towards future therapeutic application. Mediators Inflamm 2010
Odfalk K.F.; Bieniek K.F.; Hopp S.C.; Microglia: Friend and foe in tauopathy. Prog Neurobiol 2022,216,102306 PubMed DOI
Cai Z.; Hussain M.D.; Yan L.J.; Microglia, neuroinflammation, and beta-amyloid protein in Alzheimer’s disease. Int J Neurosci 2014,124(5),307-321 PubMed DOI
Kraft A.D.; Harry G.J.; Features of microglia and neuroinflammation relevant to environmental exposure and neurotoxicity. Int J Environ Res Public Health 2011,8(7),2980-3018 PubMed DOI
Colonna M.; Butovsky O.; Microglia function in the central nervous system during health and neurodegeneration. Annu Rev Immunol 2017,35(1),441-468 PubMed DOI
Gao S.; Tan H.; Li D.; Oridonin suppresses gastric cancer -7901 cell proliferation by targeting the -alpha/androgen receptor/ -beta signalling pathway axis. J Cell Mol Med 2023,27(18),2661-2674 PubMed DOI
Gao S.; Gang J.; Yu M.; Xin G.; Tan H.; Computational analysis for identification of early diagnostic biomarkers and prognostic biomarkers of liver cancer based on GEO and TCGA databases and studies on pathways and biological functions affecting the survival time of liver cancer. BMC Cancer 2021,21(1),791 PubMed DOI
Gao S.; Tan H.; Gang J.; Inhibition of hepatocellular carcinoma cell proliferation through regulation of the cell cycle, age-rage, and leptin signaling pathways by a compound formulation comprised of andrographolide, wogonin, and oroxylin a derived from andrographis paniculata(Burm.f.) Nees. J Ethnopharmacol 2024,329,118001 PubMed DOI
Bak L.K.; Schousboe A.; Waagepetersen H.S.; The glutamate/GABA-glutamine cycle: Aspects of transport, neurotransmitter homeostasis and ammonia transfer. J Neurochem 2006,98(3),641-653 PubMed DOI
González-Reyes R.E.; Nava-Mesa M.O.; Vargas-Sánchez K.; Ariza-Salamanca D.; Mora-Muñoz L.; Involvement of astrocytes in Alzheimer’s disease from a neuroinflammatory and oxidative stress perspective. Front Mol Neurosci 2017,10,427 PubMed DOI
Maruszak A.; Żekanowski C.; Mitochondrial dysfunction and Alzheimer’s disease. Prog Neuropsychopharmacol Biol Psychiatry 2011,35(2),320-330 PubMed DOI
Rubio-Perez J.M.; Morillas-Ruiz J.M.; A review: Inflammatory process in Alzheimer’s disease, role of cytokines. ScientificWorldJournal 2012,2012,1-15 PubMed DOI
DiSabato D.J.; Quan N.; Godbout J.P.; Neuroinflammation: The devil is in the details. J Neurochem 2016,139(S2)(Suppl. 2),136-153 PubMed DOI
Blennow K.; Davidsson P.; Wallin A.; Ekman R.; Chromogranin A in cerebrospinal fluid: A biochemical marker for synaptic degeneration in Alzheimer’s disease? Dementia 1995,6(6),306-311 PubMed
Clayton K.; Delpech J.C.; Herron S.; Iwahara N.; Ericsson M.; Saito T.; Saido T.C.; Ikezu S.; Ikezu T.; Plaque associated microglia hyper-secrete extracellular vesicles and accelerate tau propagation in a humanized APP mouse model. Mol Neurodegener 2021,16(1),18 PubMed DOI
Karch C.M.; Goate A.M.; Alzheimer’s disease risk genes and mechanisms of disease pathogenesis. Biol Psychiatry 2015,77(1),43-51 PubMed DOI
Navarro V.; Sanchez-Mejias E.; Jimenez S.; Muñoz-Castro C.; Sanchez-Varo R.; Davila J.C.; Vizuete M.; Gutierrez A.; Vitorica J.; Microglia in Alzheimer’s disease: Activated, dysfunctional or degenerative. Front Aging Neurosci 2018,10,140 PubMed DOI
Doorn K.J.; Goudriaan A.; Blits-Huizinga C.; Bol J.G.J.M.; Rozemuller A.J.; Hoogland P.V.J.M.; Lucassen P.J.; Drukarch B.; van de Berg W.D.J.; van Dam A.M.; Increased amoeboid microglial density in the olfactory bulb of Parkinson’s and Alzheimer’s patients. Brain Pathol 2014,24(2),152-165 PubMed DOI
Tischer J.; Krueger M.; Mueller W.; Staszewski O.; Prinz M.; Streit W.J.; Bechmann I.; Inhomogeneous distribution of Iba-1 characterizes microglial pathology in Alzheimer’s disease. Glia 2016,64(9),1562-1572 PubMed DOI
Streit W.J.; Braak H.; Xue Q.S.; Bechmann I.; Dystrophic (senescent) rather than activated microglial cells are associated with tau pathology and likely precede neurodegeneration in Alzheimer’s disease. Acta Neuropathol 2009,118(4),475-485 PubMed DOI
Sanchez-Mejias E.; Navarro V.; Jimenez S.; Sanchez-Mico M.; Sanchez-Varo R.; Nuñez-Diaz C.; Trujillo-Estrada L.; Davila J.C.; Vizuete M.; Gutierrez A.; Vitorica J.; Soluble phospho-tau from Alzheimer’s disease hippocampus drives microglial degeneration. Acta Neuropathol 2016,132(6),897-916 PubMed DOI
Leng F.; Edison P.; Neuroinflammation and microglial activation in Alzheimer disease: Where do we go from here? Nat Rev Neurol 2021,17(3),157-172 PubMed DOI
Leitner G.R.; Wenzel T.J.; Marshall N.; Gates E.J.; Klegeris A.; Targeting toll-like receptor 4 to modulate neuroinflammation in central nervous system disorders. Expert Opin Ther Targets 2019,23(10),865-882 PubMed DOI
Zaffaroni L.; Peri F.; Recent advances on Toll-like receptor 4 modulation: New therapeutic perspectives. Future Med Chem 2018,10(4),461-476 PubMed DOI
Pérez-Regidor L.; Guzmán-Caldentey J.; Oberhauser N.; Punzón C.; Balogh B.; Pedro J.R.; Falomir E.; Nurisso A.; Mátyus P.; Menéndez J.C.; de Andrés B.; Fresno M.; Martín-Santamaría S.; Small molecules as toll-like receptor 4 modulators drug and in-house computational repurposing. Biomedicines 2022,10(9),2326 PubMed DOI
Zusso M.; Lunardi V.; Franceschini D.; Pagetta A.; Lo R.; Stifani S.; Frigo A.C.; Giusti P.; Moro S.; Ciprofloxacin and levofloxacin attenuate microglia inflammatory response via TLR4/NF-kB pathway. J Neuroinflammation 2019,16(1),148 PubMed DOI
Zhang Y.; Liang X.; Bao X.; Xiao W.; Chen G.; Toll- like receptor 4 (TLR4) inhibitors: Current research and prospective. Eur J Med Chem 2022,235,114291 PubMed DOI
Verma R.K.; Chawla P.; Pandey M.; Choudhury H.; Mayuren J.; Bhattamisra S.K.; Gorain B.; Raja M.A.G.; Amjad M.W.; Obaidur Rahman S.; An insight into the role of artificial intelligence in the early diagnosis of Alzheimer’s disease. CNS Neurol Disord Drug Targets 2022,21(10),901-912 PubMed DOI
Chawla P.A.; Kumar A.; Nehra B.; Singh D.; Kumar D.; Recent advances in the development of nitrogen-containing heterocyclic anti-Alzheimer’s agents. Curr Top Med Chem 2023,23(13),1277-1306 PubMed DOI