Mitochondrial aging and dysfunction in Alzheimer's disease.
Disruptions in energy metabolism have been suggested to be a prominent feature, perhaps even a fundamental component, of Alzheimer's disease (AD). These abnormalities in cerebral metabolism precede the onset of neurological dysfunction as well as gross neuropathology of AD. These changes may stem from inhibition of mitochondrial enzymes including pyruvate dehydrogenase, cytochrome c oxidase, and alpha-ketoglutarate dehydrogenase. Several lines of evidence also suggest a role for oxidative stress in the neuropathology associated with the disease state. Because mitochondria are the major site of free radical production in cells, they are also a primary target for oxidative damage and subsequent dysfunction. This link between mitochondrial dysfunction and the pathophysiology of AD is supported by several lines of evidence.
Sullivan
Patrick G
PG
University of Kentucky, Spinal Cord and Brain Injury Research Center (SCoBIRC), Lexington, KY 40536-0305, USA. PatSull@uky.edu
Brown
Maile R
MR
D000375:Aging / Q000502:physiology*; D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000502:physiology*; D013997:Time Factors