摘要
Oxidative phosphorylation is a source of energy production by which many cells satisfy their energy requirements. Endogenous reactive oxygen species (ROS) are by-products of oxidative phosphorylation. ROS are formed due to the inefficiency of oxidative phosphorylation, and lead to oxidative stress that affects mitochondrial metabolism. Chronic oxidative stress contributes to the onset of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS). The immediate consequences of oxidative stress include lipid peroxidation, protein oxidation, and mitochondrial deoxyribonucleic acid (mtDNA) mutation, which induce neuronal cell death. Mitochondrial binding of amyloid-β (Aβ) protein has been identified as a contributing factor in AD. In PD and HD, respectively, α-synuclein (α-syn) and huntingtin (Htt) gene mutations have been reported to exacerbate the effects of oxidative stress. Similarly, abnormalities in mitochondrial dynamics and the respiratory chain occur in ALS due to dysregulation of mitochondrial complexes II and IV. However, oxidative stress-induced dysfunctions in neurodegenerative diseases can be mitigated by the antioxidant function of hydrogen sulfide (H2S), which also acts through the potassium (KATP/K+) ion channel and calcium (Ca2+) ion channels to increase glutathione (GSH) levels. The pharmacological activity of H2S is exerted by both inorganic and organic compounds. GSH, glutathione peroxidase (Gpx), and superoxide dismutase (SOD) neutralize H2O2-induced oxidative damage in mitochondria. The main purpose of this review is to discuss specific causes and effects of mitochondrial oxidative stress in neurodegenerative diseases, and how these are impacted by the antioxidant functions of H2S to support the development of advancements in neurodegenerative disease treatment.
摘要译文
氧化磷酸化是产生能量的一种来源，许多细胞可以通过这些来源满足其能量需求。内源性活性氧（ROS）是氧化磷酸化的副产物。 ROS是由于氧化磷酸化的效率低下而形成的，并导致影响线粒体代谢的氧化应激。慢性氧化应激会导致神经退行性疾病的发作，例如阿尔茨海默氏病（AD），帕金森氏病（PD），亨廷顿氏病（HD）和肌萎缩性侧索硬化症（ALS）。氧化应激的直接后果包括脂质过氧化，蛋白质氧化和线粒体脱氧核糖核酸（mtDNA）突变，这些突变可诱导神经元细胞死亡。淀粉样蛋白-β（Aβ）蛋白的线粒体结合已被确定为AD的促成因素。据报道，在PD和HD中，α-突触核蛋白（α-syn）和亨廷顿蛋白（Htt）基因突变加剧了氧化应激的作用。同样，由于线粒体复合物II和IV的失调，ALS中发生了线粒体动力学和呼吸链异常。然而，硫化氢（H 2 S）的抗氧化功能可以缓解氧化应激所致的神经退行性疾病，硫化氢也可以通过钾离子（K ATP / K + ）和钙起作用（Ca 2 + ）离子通道可增加谷胱甘肽（GSH）水平。 H 2 S的药理活性由无机和有机化合物共同发挥。谷胱甘肽，谷胱甘肽过氧化物酶（Gpx）和超氧化物歧化酶（SOD）中和H 2 O 2引起的线粒体氧化损伤。这篇综述的主要目的是讨论神经退行性疾病中线粒体氧化应激的具体原因和影响，以及H 2 S的抗氧化功能如何影响线粒体氧化应激以支持神经退行性疾病治疗进展的发展。
Rubaiya Tabassum; Na Young Jeong. Potential for therapeutic use of hydrogen sulfide in oxidative stress-induced neurodegenerative diseases[J]. International Journal of Medical Sciences, 2019,16(10): 1386-1396