title: Mitochondrial permeability transition pore in Alzheimer's disease: cyclophilin D and amyloid beta.
abstract: Amyloid beta (Abeta) plays a critical role in the pathophysiology of Alzheimer's disease. Increasing evidence indicates mitochondria as an important target of Abeta toxicity; however, the effects of Abeta toxicity on mitochondria have not yet been fully elucidated. Recent biochemical studies in vivo and in vitro implicate mitochondrial permeability transition pore (mPTP) formation involvement in Abeta-mediated mitochondrial dysfunction. mPTP formation results in severe mitochondrial dysfunction such as reactive oxygen species (ROS) generation, mitochondrial membrane potential dissipation, intracellular calcium perturbation, decrease in mitochondrial respiration, release of pro-apoptotic factors and eventually cell death. Cyclophilin D (CypD) is one of the more well-known mPTP components and recent findings reveal that Abeta has significant impact on CypD-mediated mPTP formation. In this review, the role of Abeta in the formation of mPTP and the potential of mPTP inhibition as a therapeutic strategy in AD treatment are examined.
authors.affiliation: Departments of Pathology and Cell Biology, Surgery, and The Taub institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons of Columbia University, 630 W. 168th Street, New York, NY 10032, USA.
authors.forename: Heng
authors.initials: H
authors.lastname: Du
authors.forename: Shirley ShiDu
authors.initials: SS
authors.lastname: Yan
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism*; D000083162:Mitochondrial Permeability Transition Pore
chemical_list: D016229:Amyloid beta-Peptides; D000081406:Peptidyl-Prolyl Isomerase F; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D021983:Cyclophilins