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An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure

1
Instituto de Ciencias Físicas, Universidad Nacional Autónoma de México, Cuernavaca 62210, Mexico
2
Department of Biosystems and Soft Matter, Institute of Fundamental Technological Research Polish Academy of Science, Pawińskiego 5B, 02-106 Warsaw, Poland
3
International Center for Research on Innovative Biobased Materials (ICRI-BioM)—International Research Agenda, Lodz University of Technology, Zeromskiego 116, 90-924 Lodz, Poland
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2021, 22(19), 10798; https://doi.org/10.3390/ijms221910798
Received: 28 August 2021 / Revised: 1 October 2021 / Accepted: 3 October 2021 / Published: 6 October 2021
(This article belongs to the Section Molecular Neurobiology)
Amyloid beta (Aβ) oligomers are the most neurotoxic aggregates causing neuronal death and cognitive damage. A detailed elucidation of the aggregation pathways from oligomers to fibril formation is crucial to develop therapeutic strategies for Alzheimer’s disease (AD). Although experimental techniques rely on the measure of time- and space-average properties, they face severe difficulties in the investigation of Aβ peptide aggregation due to their intrinsically disorder character. Computer simulation is a tool that allows tracing the molecular motion of molecules; hence it complements Aβ experiments, as it allows to explore the binding mechanism between metal ions and Aβ oligomers close to the cellular membrane at the atomic resolution. In this context, integrated studies of experiments and computer simulations can assist in mapping the complete pathways of aggregation and toxicity of Aβ peptides. Aβ oligomers are disordered proteins, and due to a rapid exploration of their intrinsic conformational space in real-time, they are challenging therapeutic targets. Therefore, no good drug candidate could have been identified for clinical use. Our previous investigations identified two small molecules, M30 (2-Octahydroisoquinolin-2(1H)-ylethanamine) and Gabapentin, capable of Aβ binding and inhibiting molecular aggregation, synaptotoxicity, intracellular calcium signaling, cellular toxicity and memory losses induced by Aβ. Thus, we recommend these molecules as novel candidates to assist anti-AD drug discovery in the near future. This review discusses the most recent research investigations about the Aβ dynamics in water, close contact with cell membranes, and several therapeutic strategies to remove plaque formation. View Full-Text
Keywords: Alzheimer’s disease; amyloid β peptide; plaque formation; small molecules; M30; gabapentin; MD simulation Alzheimer’s disease; amyloid β peptide; plaque formation; small molecules; M30; gabapentin; MD simulation
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MDPI and ACS Style

Boopathi, S.; Poma, A.B.; Garduño-Juárez, R. An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure. Int. J. Mol. Sci. 2021, 22, 10798. https://doi.org/10.3390/ijms221910798

AMA Style

Boopathi S, Poma AB, Garduño-Juárez R. An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure. International Journal of Molecular Sciences. 2021; 22(19):10798. https://doi.org/10.3390/ijms221910798

Chicago/Turabian Style

Boopathi, Subramanian, Adolfo B. Poma, and Ramón Garduño-Juárez. 2021. "An Overview of Several Inhibitors for Alzheimer’s Disease: Characterization and Failure" International Journal of Molecular Sciences 22, no. 19: 10798. https://doi.org/10.3390/ijms221910798

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