Abstract
Mitochondrial dysfunction has been implicated in causing metabolic abnormalities in Alzheimers disease (AD). The searches for mitochondrial DNA variants associated with AD susceptibility have generated conflicting results. The age-related accumulation of somatic mitochondrial DNA deletion has been suggested to play a pathogenic role in the development of AD. Recent studies have demonstrated that amyloid-beta peptide (Aβ) progressively accumulates in mitochndrial matrix, as demonstrated in both transgenic mice over-expressing mutant amyloid precursor protein (APP) and autopsy brain from AD patients. Aβ-mediated mitochondrial stress was evidenced by impaired oxygen consumption and decreased respiratory chain complexes III and IV activities in brains from AD patients and AD-type transgenic mouse model. Furthermore, our studies indicated that interaction of intramitochondrial Aβ with a mitochondrial enzyme, amyloid binding alcohol dehydrogenase (ABAD), inhibits its enzyme activity, enhances generation of reactive oxygen species (ROS), impairs energy metabolism, and exaggerates Aβ-induced spatial learning/memory deficits and neuropathological changes in transgenic AD-type mouse model. Interception of ABAD-Aβ interaction may be a potential therapeutic strategy for Alzheimers disease.
Keywords: cytochrome c oxidase (COX), reactive oxygen species (ROS), AD-specific mtDNA variants, amyloid precursor protein, ABAD interaction
Current Alzheimer Research
Title: Mitochondrial Dysfunction and Alzheimers Disease
Volume: 3 Issue: 5
Author(s): Xi Chen, David Stern and Shi Du Yan
Affiliation:
Keywords: cytochrome c oxidase (COX), reactive oxygen species (ROS), AD-specific mtDNA variants, amyloid precursor protein, ABAD interaction
Abstract: Mitochondrial dysfunction has been implicated in causing metabolic abnormalities in Alzheimers disease (AD). The searches for mitochondrial DNA variants associated with AD susceptibility have generated conflicting results. The age-related accumulation of somatic mitochondrial DNA deletion has been suggested to play a pathogenic role in the development of AD. Recent studies have demonstrated that amyloid-beta peptide (Aβ) progressively accumulates in mitochndrial matrix, as demonstrated in both transgenic mice over-expressing mutant amyloid precursor protein (APP) and autopsy brain from AD patients. Aβ-mediated mitochondrial stress was evidenced by impaired oxygen consumption and decreased respiratory chain complexes III and IV activities in brains from AD patients and AD-type transgenic mouse model. Furthermore, our studies indicated that interaction of intramitochondrial Aβ with a mitochondrial enzyme, amyloid binding alcohol dehydrogenase (ABAD), inhibits its enzyme activity, enhances generation of reactive oxygen species (ROS), impairs energy metabolism, and exaggerates Aβ-induced spatial learning/memory deficits and neuropathological changes in transgenic AD-type mouse model. Interception of ABAD-Aβ interaction may be a potential therapeutic strategy for Alzheimers disease.
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Cite this article as:
Chen Xi, Stern David and Du Yan Shi, Mitochondrial Dysfunction and Alzheimers Disease, Current Alzheimer Research 2006; 3 (5) . https://dx.doi.org/10.2174/156720506779025215
DOI https://dx.doi.org/10.2174/156720506779025215 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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