Reddy P Hemachandra
Oregon National Primate Research Center, Oregon Health & Science University, Beaverton, OR 97006, USA.
Biochim Biophys Acta. 2013 Jan;1832(1):67-75. doi: 10.1016/j.bbadis.2012.09.003. Epub 2012 Sep 17.
Mitochondrial dysfunction and synaptic damage have been described as early events in Alzheimer's disease (AD) pathogenesis. Recent research using AD postmortem brains, and AD mouse and cell models revealed that amyloid beta (Aβ) and tau hyperphosphorylation are involved in mitochondrial dysfunction and synaptic damage in AD. Further, recent research also revealed that the protein levels of mitochondrial outer membrane protein, voltage-dependent anion channel 1 (VDAC1), are elevated in the affected regions of AD postmortem brains and cortical tissues from APP transgenic mice. In addition, emerging research using AD postmortem brains and AD mouse models revealed that VDAC1 is linked to Aβ and phosphorylated tau, blocks the mitochondrial permeability transition (MPT) pores, disrupts the transport of mitochondrial proteins and metabolites, impairs gating of VDAC, and causes defects in oxidative phosphorylation, leading to mitochondrial dysfunction in AD neurons. The purpose of this article is to review research that has investigated the relationship between VDAC1 and the regulation of MPT pores in AD progression.
线粒体功能障碍和突触损伤被认为是阿尔茨海默病（AD）发病机制中的早期事件。最近使用AD死后大脑、AD小鼠和细胞模型的研究表明，淀粉样β蛋白（Aβ）和tau蛋白过度磷酸化与AD中的线粒体功能障碍和突触损伤有关。此外，最近的研究还表明，线粒体外膜蛋白电压依赖性阴离子通道1（VDAC1）的蛋白水平在AD死后大脑和APP转基因小鼠皮质组织的受影响区域升高。此外，使用AD死后大脑和AD小鼠模型的新研究表明，VDAC1与Aβ和磷酸化tau蛋白有关，阻断线粒体通透性转换（MPT）孔，破坏线粒体蛋白和代谢物的运输，损害VDAC的门控，并导致氧化磷酸化缺陷，从而导致AD神经元中的线粒体功能障碍。本文的目的是综述研究VDAC1与AD进展中MPT孔调节之间关系的研究。
