Mitochondrial permeability transition pore in Alzheimer's disease: Cyclophilin D and amyloid beta

Amyloid beta (A beta) plays a critical role in the pathophysiology of Alzheimer's disease. increasing evidence indicates mitochondria as an important target of A beta toxicity; however, the effects of A beta 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 A beta-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 A beta has significant impact on CypD-mediated mPTP formation. In this review, the role of A beta in the formation of mPTP and the potential of mPTP inhibition as a therapeutic strategy in AD treatment are examined. (C) 2009 Elsevier B.V. All rights reserved.