Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA.
Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan 816513-1378, Iran.
Mitochondrion. 2018 Sep;42:77-83. doi: 10.1016/j.mito.2017.12.002. Epub 2017 Dec 8.
Onset of Alzheimer's, Parkinson's and Huntington's diseases as neurodegenerative disorders is increased by age. Alleviation of clinical symptoms and protection of neurons against degeneration are the main aspects of researches to establish new therapeutic strategies. Many studies have shown that mitochondria play crucial roles in high energy demand tissues like brain. Impairments in mitochondrial activity and physiology can makes neurons vulnerable to stress and degeneration. Succinate dehydrogenase (SDH) connects tricarboxylic cycle to the electron transport chain. Therefore, dysfunction of the SDH could impair mitochondrial activity, ATP generation and energy hemostasis in the cell. Exceed lipid synthesis, induction of the excitotoxicity in neurodegenerative disorders could be controlled by SDH through direct and indirect mechanism. In addition, mutation in SDH correlates with the onset of neurodegenerative disorders. Therefore, SDH could behave as a key regulator in neuroprotection. This review will present recent findings which are about SDH activity and related pathways which could play important roles in neuronal survival. Additionally, we will discuss about all possibilities which candidate SDH as a neuroprotective agent.
阿尔茨海默病、帕金森病和亨廷顿病等神经退行性疾病的发病与年龄有关。缓解临床症状和保护神经元免受变性是建立新治疗策略的主要研究方向。许多研究表明，线粒体在大脑等高能量需求组织中起着至关重要的作用。线粒体活性和生理学的损伤会使神经元易受应激和变性的影响。琥珀酸脱氢酶（SDH）将三羧酸循环与电子传递链连接起来。因此，SDH 的功能障碍可能会损害细胞中线粒体的活性、ATP 的生成和能量平衡。通过直接和间接机制，SDH 可以控制神经退行性疾病中超脂质合成和兴奋性毒性的诱导。此外，SDH 的突变与神经退行性疾病的发病有关。因此，SDH 可以作为神经保护的关键调节剂。本综述将介绍最近关于 SDH 活性及其相关途径的发现，这些发现可能在神经元存活中发挥重要作用。此外，我们还将讨论将 SDH 作为神经保护剂的所有可能性。
