Applied Biology, CSIR-Indian Institute of Chemical Technology, Hyderabad, India.
Department of Physics, National Institute of Technology-Warangal, Warangal, India.
J Neurosci Res. 2021 Apr;99(4):1120-1135. doi: 10.1002/jnr.24781. Epub 2021 Jan 19.
Alzheimer's disease (AD) is the most common type of dementia and progressive neurodegenerative disease. The presence of β-amyloid (Aβ) plaques and phosphorylated Tau tangles are considered to be the two main hallmarks of AD. Recent findings have shown that different changes in the structure and dynamics of mitochondria play an important role in AD pathology progression. Mitochondrial changes in AD are expressed as enhanced mitochondrial fragmentation, altered mitochondrial dynamics, and changes in the expression of mitochondrial biogenesis genes in vitro and in vivo models. Therefore, targeting mitochondria and associated mitochondrial proteins seems to be a promising alternative instead of targeting Aβ and Tau in the prevention of Alzheimer's disease. The dynamin-related protein (Drp1) is one such protein that plays an important role in the regulation of mitochondrial division and maintenance of mitochondrial structures. Few researchers have shown that inhibition of Drp1 GTPase activity in neuronal cells rescues excessive mitochondrial fragmentation. In addition, the growing evidence revealed that Drp1 can interact with both Aβ and Tau protein in human brain tissues and mouse models. In this review, we would like to update existing knowledge about various changes in and around mitochondria related to the pathogenesis of Alzheimer's disease, with particular emphasis on mitophagy and autophagy.
阿尔茨海默病（AD）是最常见的痴呆症和进行性神经退行性疾病。β-淀粉样蛋白（Aβ）斑块和磷酸化 Tau 缠结的存在被认为是 AD 的两个主要标志。最近的研究结果表明，线粒体结构和动态的不同变化在 AD 病理进展中起着重要作用。AD 中的线粒体变化表现为增强的线粒体碎片化、线粒体动力学改变以及体外和体内模型中线粒体生物发生基因表达的变化。因此，靶向线粒体及其相关的线粒体蛋白似乎是一种有前途的替代方法，而不是在预防阿尔茨海默病时靶向 Aβ 和 Tau。与线粒体分裂和维持线粒体结构有关的动力相关蛋白 1（Drp1）就是这样一种蛋白。一些研究人员已经表明，抑制神经元细胞中的 Drp1 GTPase 活性可以挽救过度的线粒体碎片化。此外，越来越多的证据表明，Drp1 可以与人类脑组织和小鼠模型中的 Aβ 和 Tau 蛋白相互作用。在这篇综述中，我们将更新与阿尔茨海默病发病机制相关的线粒体及其周围各种变化的现有知识，特别强调自噬和自噬。
