Amyloid oligomers: formation and toxicity of Aβ oligomers

被引：500

作者：

Sakono, Masafumi ^{[1
,2
]}

Zako, Tamotsu ^{[1
]}

机构：

[1] Riken Inst Phys & Chem Res, Bioengn Lab, Wako, Saitama 3510198, Japan

[2] Japan Sci & Technol Agcy, PRESTO, Kawaguchi, Saitama, Japan

来源：

FEBS JOURNAL | 2010年 / 277卷 / 06期

关键词：

Alzheimer's disease; amyloid beta; formation and toxicity mechanism; intracellular and extracellular oligomers; soluble amyloid oligomers; NEUROTROPHIN RECEPTOR PROTECTS; LONG-TERM POTENTIATION; GROUP-II CHAPERONIN; ALZHEIMERS-DISEASE; CYTOSOLIC CHAPERONIN; MOLECULAR CHAPERONES; SOLUBLE OLIGOMERS; OXIDATIVE STRESS; ALPHA-SYNUCLEIN; NERVOUS-SYSTEM;

D O I：

10.1111/j.1742-4658.2010.07568.x

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Alzheimer's disease (AD) is an age-related, progressive degenerative disorder that is characterized by synapse and neuron loss in the brain and the accumulation of protein-containing deposits (referred to as 'senile plaques') and neurofibrillary tangles. Insoluble amyloid beta-peptide (A beta) fibrillar aggregates found in extracellular plaques have long been thought to cause the neurodegenerative cascades of AD. However, accumulating evidence suggests that prefibrillar soluble A beta oligomers induce AD-related synaptic dysfunction. The size of A beta oligomers is distributed over a wide molecular weight range (from < 10 kDa to > 100 kDa), with structural polymorphism in A beta oligomers of similar sizes. Recent studies have demonstrated that A beta can accumulate in living cells, as well as in extracellular spaces. This review summarizes current research on A beta oligomers, focusing on their structures and toxicity mechanism. We also discuss possible formation mechanisms of intracellular and extracellular A beta oligomers.

引用

页码：1348 / 1358

页数：11

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