Mitochondrial permeability transition pore is a potential drug target for neurodegeneration

article Mitochondrial permeability transition pore (mPTP) plays a central role in alterations of mitochondrial structure and function leading to neuronal injury relevant to aging and neurodegenerative diseases including Alzheimer's disease (AD). mPTP putatively consists of the voltage-dependent anion channel (VDAC), the adenine nucleotide translocator (ANT) and cyclophilin D (CypD). Reactive oxygen species (ROS) increase intra-cellular calcium and enhance the formation of mPTP that leads to neuronal cell death in AD. CypD-dependent mPTP can play a crucial role in ischemia/reperfusion injury. The interaction of amyloid beta peptide (Aβ) with CypD potentiates mito- chondrial and neuronal perturbation. This interaction triggers the formation of mPTP, resulting in decreased mi- tochondrialmembrane potential,impairedmitochondrialrespiration function,increasedoxidativestress,release of cytochrome c, and impaired axonal mitochondrial transport. Thus, the CypD-dependent mPTP is directly linked to the cellular and synaptic perturbations observed in the pathogenesis of AD. Designing small molecules toblock thisinteractionwouldlessenthe effectsof Aβneurotoxicity.Thisreviewsummarizesthe recentprogress on mPTP and its potential therapeutic target for neurodegenerative diseases including AD. This article is part of a