Unlocking the Door to Neuronal Woes in Alzheimer’s Disease Aβ and Mitochondrial Permeability Transition Pore 英文参考文献.docVIP

Pharmaceuticals 2010, 3, 1936-1948; doi:10.3390/ph3061936 OPEN ACCESS pharmaceuticals ISSN 1424-8247 /journal/pharmaceuticals Review Unlocking the Door to Neuronal Woes in Alzheimer’s Disease: Aβ and Mitochondrial Permeability Transition Pore Heng Du 1and Shirley ShiDu Yan 1,2,3, * 1 Department of Surgery, Physicians Surgeons College of Columbia University, New York, NY 10032, USA 2 Department of Pathology Cell Biology, Physicians Surgeons College of Columbia University, New York, NY 10032, USA 3 The Taub institute for Research on Alzheimer’s Disease and the Aging Brain, Columbia University, New York, NY 10032, USA * Author to whom correspondence should be addressed; E-Mail: sdy1@; Tel.: +1-212 342 1304. Received: 10 May 2010; in revised form: 10 June 2010 / Accepted: 14 June 2010 / Published: 14 June 2010 Abstract: Mitochondrial dysfunction occurs early in the progression of Alzheimer’s disease. Amyloid-β peptide has deleterious effects on mitochondrial function and contributes to energy failure, respiratory chain impairment, neuronal apoptosis, and generation of reactive oxygen species in Alzheimer’s disease. The mechanisms underlying amyloid-β induced mitochondrial stress remain unclear. Emerging evidence indicates that mitochondrial permeability transition pore is important for maintenance of mitochondrial and neuronal function in aging and neurodegenerative disease. Cyclophilin D (Cyp D) plays a central role in opening mitochondrial permeability transition pore, ultimately leading to cell death. Interaction of amyloid-β with cyclophilin D triggers or enhances the formation of mitochondrial permeability transition pores, consequently exacerbating mitochondrial and neuronal dysfunction, as shown by decreased mitochondrial membrane potential, impaired mitochondrial respiration function, and increased oxidative stress and cytochrome c release