title: Mitochondrial dysfunction in aging and Alzheimer's disease: strategies to protect neurons.
abstract: Recent structural and functional studies of mitochondria have revealed that abnormalities in mitochondria may lead to mitochondrial dysfunction in aged individuals and those with neurodegenerative diseases, including Alzheimer's disease (AD). Molecular, cellular, and biochemical studies of animal models of aging and AD have provided compelling evidence that mitochondria are involved in AD development and progression. Further, a role for mitochondrial dysfunction in AD is supported by studies of neurons from autopsy specimens of patients with AD, transgenic AD mice, and neuronal cells expressing human AD mutation, which have revealed that amyloid beta (Abeta) enters mitochondria early in the disease process and disrupts the electron-transport chain, generates reactive oxygen species, and inhibits the production of cellular ATP, which in turn prevents neurons from functioning normally. Although AD researchers are actively involved in understanding Abeta toxicity and trying to develop strategies to reduce Abeta toxicity, one route they have yet to take is to investigate the molecules that activate nonamyloidogenic alpha-secretase activity that may reduce Abeta production and toxicity. In addition, it may be worthwhile to develop mitochondrially targeted antioxidants to treat AD. This article discusses critical issues of mitochondria causing dysfunction in aging and AD and discusses the strategies to protect neurons caused by mitochondrial dysfunction.
authors: Neurogenetics Laboratory, Neurological Sciences Institute, Oregon Health & Science University, Beaverton, Oregon 97006, USA. reddyh@ohsu.edu
authors: P Hemachandra
authors: PH
authors: Reddy
mesh_terms: D000375:Aging / Q000473:pathology / Q000502:physiology*; D000544:Alzheimer Disease / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species