Mitochondrial permeability transition pore is a potential drug target for neurodegeneration.
Mitochondrial permeability transition pore is a potential drug target for neurodegeneration.
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DOI：
10.1016/j.bbadis.2013.09.003
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发表时间：
2014-08
影响因子：
6.2
通讯作者：
Yan, Shirley Shidu
中科院分区：
文献类型：
--
作者：
Rao, Valasani Koteswara;Carlson, Emily A.;Yan, Shirley Shidu
关键词：
线粒体通透性过渡孔（mPTP）在线粒体结构和功能改变中起核心作用，导致与衰老和神经退行性疾病（包括阿尔茨海默病（AD））相关的神经元损伤。mPTP由电压依赖性阴离子通道（VDAC）和腺嘌呤核苷酸转运体（ANT）组成。亲环蛋白D （CypD）和活性氧（ROS）增加细胞内钙，促进mPTP的形成，导致AD神经元细胞死亡。cypd依赖性mPTP在缺血/再灌注损伤中发挥重要作用。淀粉样蛋白β肽（Aβ）与CypD的相互作用增强了线粒体和神经元的扰动。这种相互作用触发mPTP的形成，导致线粒体膜电位下降，线粒体呼吸功能受损，氧化应激增加，细胞色素c释放，轴突线粒体运输受损。因此，cypd依赖性mPTP与阿尔茨海默病发病过程中观察到的细胞和突触扰动直接相关。设计小分子来阻断这种相互作用将减轻Aβ神经毒性的影响。本文综述了近年来mPTP的研究进展及其在AD等神经退行性疾病中的潜在治疗靶点。
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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影响因子：
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作者：
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通讯作者：
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DOI：
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