Amyloid-beta-induced mitochondrial dysfunction.
As an important molecule in the pathogenesis of Alzheimer's disease (AD), amyloid-beta (Abeta) interferes with multiple aspects of mitochondrial function, including energy metabolism failure, production of reactive oxygen species (ROS) and permeability transition pore formation. Recent studies have demonstrated that Abeta progressively accumulates within mitochondrial matrix, providing a direct link to mitochondrial toxicity. Abeta-binding alcohol dehydrogenase (ABAD) is localized to the mitochondrial matrix and binds to mitochondrial Abeta. Interaction of ABAD with Abeta exaggerates Abeta-mediated mitochondrial and neuronal perturbation, leading to impaired synaptic function, and dysfunctional spatial learning/memory. Thus, blockade of ABAD/Abeta interaction may be a potential therapeutic strategy for AD.
Chen
John Xi
JX
Harvey Cushing Institutes of Neuroscience, North Shore-Long Island Jewish Health System, Great Neck, NY 11021, USA.
Yan
Shi Du
SD
D000544:Alzheimer Disease / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D004734:Energy Metabolism; D006801:Humans; D028361:Mitochondrial Diseases / Q000453:epidemiology / Q000378:metabolism / Q000503:physiopathology
D016564:Amyloid beta-Protein Precursor