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

被引：187

作者：

Doig, Andrew J. ^{[1
,2
]}

del Castillo-Frias, Maria P. ^{[1
,2
]}

Berthoumieu, Olivia ^{[3
,4
]}

Tarus, Bogdan ^{[5
]}

Nasica-Labouze, Jessica ^{[5
]}

Sterpone, Fabio ^{[5
]}

Nguyen, Phuong H. ^{[5
]}

Hooper, Nigel M. ^{[6
]}

Faller, Peter ^{[3
,4
]}

Derreumaux, Philippe ^{[5
]}

机构：

[1] Univ Manchester, Dept Chem, 131 Princess St, Manchester M7 1DN, Lancs, England

[2] Univ Manchester, Fac Sci & Engn, Manchester Inst Biotechnol, 131 Princess St, Manchester M7 1DN, Lancs, England

[3] Univ Strasbourg, Inst Chim, UMR7177, Biomat & Biol Chem, 4 Rue B Pascal, F-67081 Strasbourg, France

[4] CNRS, Lab Chim Coordinat, 205 Route Narbonne, F-31077 Toulouse, France

[5] Univ Paris Diderot, Sorbonne Paris Cite, Lab Biochim Theor, UPR 9080,CNRS,IBPC, 13 Rue Pierre & Marie Curie, F-75005 Paris, France

[6] Univ Manchester, Fac Biol Med & Hlth, Sch Biol Sci, Div Neurosci & Expt Psychol, Oxford Rd, Manchester M13 9PT, Lancs, England

来源：

ACS CHEMICAL NEUROSCIENCE | 2017年 / 8卷 / 07期

关键词：

Amyloid-beta; Alzheimer's disease; in vitro and in vivo studies; computer simulations; drugs; PROTEIN;

D O I：

10.1021/acschemneuro.7b00188

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

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-beta (A beta) peptides, primarily A beta 1-40 and A beta 1-42. Targeting the production, aggregation, and toxicity of A beta 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 A beta 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.

引用

页码：1435 / 1437

页数：3

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