Why Is Research on Amyloid-β Failing to Give New Drugs for Alzheimer's Disease?

TitleWhy Is Research on Amyloid-β Failing to Give New Drugs for Alzheimer's Disease?
Publication TypeJournal Article
Year of Publication2017
AuthorsDoig AJ, Del Castillo-Frias MP, Berthoumieu O, Tarus B, Nasica-Labouze J, Sterpone F, Nguyen PH, Hooper NM, Faller P, Derreumaux P
JournalACS Chem Neurosci
Volume8
Issue7
Pagination1435-1437
Date Published2017 Jul 19
ISSN1948-7193
KeywordsAlzheimer Disease, Amyloid beta-Peptides, Animals, Drug Discovery, Humans, Neuroprotective Agents
Abstract

The two hallmarks of Alzheimer's disease (AD) are the presence of neurofibrillary tangles (NFT) made of aggregates of the hyperphosphorylated tau protein and of amyloid plaques composed of amyloid-β (Aβ) peptides, primarily Aβ1-40 and Aβ1-42. Targeting the production, aggregation, and toxicity of Aβ with small molecule drugs or antibodies is an active area of AD research due to the general acceptance of the amyloid cascade hypothesis, but thus far all drugs targeting Aβ have failed. From a review of the recent literature and our own experience based on in vitro, in silico, and in vivo studies, we present some reasons to explain this repetitive failure.

DOI10.1021/acschemneuro.7b00188
Alternate JournalACS Chem Neurosci
Citation Key2017|2030
PubMed ID28586203