Int J Med Sci 2019; 16(10):1386-1396. doi:10.7150/ijms.36516
Potential for therapeutic use of hydrogen sulfide in oxidative stress-induced neurodegenerative diseases
1. Department of Anatomy and Cell Biology, College of Medicine, Dong-A University, 32, Daesingongwon-ro, Seo-gu, Busan, 49201, Korea.
2. Department of Medicine, Graduate School, Dong-A University, 32, Daesingongwon-ro, Seo-gu, Busan, 49201, Korea.
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.
Keywords: central nervous system, hydrogen sulphide, mitochondrial dysfunction, neurodegenerative diseases, oxidative stress
Tabassum R, Jeong NY. Potential for therapeutic use of hydrogen sulfide in oxidative stress-induced neurodegenerative diseases. Int J Med Sci 2019; 16(10):1386-1396. doi:10.7150/ijms.36516. Available from http://www.medsci.org/v16p1386.htm