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Mitochondrial permeability transition pore is a potential drug target for neurodegeneration
Rao, Valasani Koteswara Carlson, Emily A. Yan, Shirley ShiDu
Rao, Valasani Koteswara
Carlson, Emily A.
Yan, Shirley ShiDu
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Abstract
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) and the adenine nucleotide translocator (ANT). Cyclophilin D (CypD) and 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 mitochondrial and neuronal perturbation. This interaction triggers the formation of mPTP, resulting in decreased mitochondrial membrane potential, impaired mitochondrial respiration function, increased oxidative stress, 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 to block this interaction would lessen the effects of Aβ neurotoxicity. This review summarizes the recent progress on mPTP and its potential therapeutic target for neurodegenerative diseases including AD.
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2014-08
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Association of American Medical Colleges
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Yan_2014.pdf
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Amyloid β, Alzheimer’s disease, Cyclophilin D, Mitochondrial permeability transition pore, Neurodegeneration
Citation
Rao VK, Carlson EA, Yan SS. Mitochondrial permeability transition pore is a potential drug target for neurodegeneration. Biochimica et biophysica acta. 2014;1842(8):1267-1272. doi:10.1016/j.bbadis.2013.09.003.