期刊
FASEB JOURNAL
卷 19, 期 12, 页码 2040-+出版社
WILEY
DOI: 10.1096/fj.05-3735fje
关键词
oxidative stress; transgenic mouse model of Alzheimer's disease; respiratory chain enzyme; intracellular A beta; energy metabolism
资金
- NIA NIH HHS [AG16736, P50 AG08702, P01 AG17490] Funding Source: Medline
- NINDS NIH HHS [NS 042855] Funding Source: Medline
Although amyloid-beta peptide (A beta) is the neurotoxic species implicated in the pathogenesis of Alzheimer's disease ( AD), mechanisms through which intracellular A beta impairs cellular properties, resulting in neuronal dysfunction, remain to be clarified. Here we demonstrate that intracellular A beta is present in mitochondria from brains of transgenic mice with targeted neuronal overexpression of mutant human amyloid precursor protein and AD patients. A beta progressively accumulates in mitochondria and is associated with diminished enzymatic activity of respiratory chain complexes (III and IV) and a reduction in the rate of oxygen consumption. Importantly, mitochondria-associated A beta, principally A beta 42, was detected as early as 4 months, before extensive extracellular A beta deposits. Our studies delineate a new means through which A beta potentially impairs neuronal energetics, contributing to cellular dysfunction in AD.
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