Role of Mitochondrial Amyloid-β in Alzheimer's Disease

被引:151
作者
Chen, John Xi [1 ]
Yan, Shirley Shidu [2 ,3 ]
机构
[1] Mem Sloan Kettering Canc Ctr, Dept Neurol, New York, NY 10021 USA
[2] Columbia Univ, Coll Phys & Surg, Dept Pathol & Cell Biol, New York, NY USA
[3] Columbia Univ, Coll Phys & Surg, Taub Inst Res Alzheimers Dis & Aging Brain, New York, NY USA
关键词
Alzheimer's disease; amyloid; cyclophilin; mitochondria; toxicity; CYTOCHROME-C-OXIDASE; PERMEABILITY TRANSITION PORE; INTRANEURONAL A-BETA-42 ACCUMULATION; ADENINE-NUCLEOTIDE TRANSLOCASE; DEFICIENT HIPPOCAMPAL-NEURONS; POSTERIOR CINGULATE CORTEX; PEPTIDE-BINDING PROTEIN; A-BETA; PRECURSOR PROTEIN; CYCLOPHILIN-D;
D O I
10.3233/JAD-2010-100357
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Mitochondrial dysfunction is an early feature of Alzheimer's disease (AD). Abnormalities in mitochondrial properties include impaired energy metabolism, defects in key respiratory enzyme activity/function, accumulation/generation of mitochondrial reactive oxygen species, and formation of membrane permeability transition pore. While the mechanisms underlying mitochondrial dysfunction remain incompletely understood, recent studies provide substantial evidence for the progressive accumulation of mitochondrial A beta, which directly links to mitochondria-mediated toxicity. In this review, we describe recent studies addressing the following key questions: I) Does A beta accumulate in mitochondria of AD brain and AD mouse models? 2) How does A beta gain access to the mitochondria? 3) If mitochondria are loaded with A. do they develop similar evidence of dysfunction? 4) What are the mechanisms underlying mitochondrial A beta-induced neuronal toxicity? and 5) What is the impact of interaction of mitochondrial A beta with its binding partners (cyclophilin 0 and ABAD) on mitochondrial and neuronal properties/function in an A beta milieu? The answers to these questions provide new insights into mechanisms of mitochondrial stress related to the pathogenesis of AD and information necessary for developing therapeutic strategy for AD.
引用
收藏
页码:S569 / S578
页数:10
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