Protective effect of hydrogen sulfide on oxidative stress-induced neurodegenerative diseases.

Hydrogen sulfide is an antioxidant molecule that has a wide range of biological effects against oxidative stress. Balanced oxidative stress is also vital for maintaining cellular function in biological system, where reactive oxygen species are the main source of oxidative stress. When the normal redox balance is disturbed, deoxyribonucleic acid, lipid, and protein molecules are oxidized under pathological conditions, like diabetes mellitus that leads to diabetic peripheral neuropathy. In diabetes mellitus-induced diabetic peripheral neuropathy, due to hyperglycemia, pancreatic beta cell (ß cell) shows resistance to insulin secretion. As a consequence, glucose metabolism is disturbed in neuronal cells which are distracted from providing proper cell signaling pathway. Not only diabetic peripheral neuropathy but also other central damages occur in brain neuropathy. Neurological studies regarding type 1 diabetes mellitus patients with Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis have shown changes in the central nervous system because high blood glucose levels (HbA1c) appeared with poor cognitive function. Oxidative stress plays a role in inhibiting insulin signaling that is necessary for brain function. Hydrogen sulfide exhibits antioxidant effects against oxidative stress, where cystathionine ß synthase, cystathionine γ lyase, and 3-mercaptopyruvate sulfurtransferase are the endogenous sources of hydrogen sulfide. This review is to explore the pathogenesis of diabetes mellitus-induced diabetic peripheral neuropathy and other neurological comorbid disorders under the oxidative stress condition and the anti-oxidative effects of hydrogen sulfide.

Therapeutic importance of hydrogen sulfide in age-associated neurodegenerative diseases.

Hydrogen sulfide (H2S) is a gasotransmitter that acts as an antioxidant and exhibits a wide variety of cytoprotective and physiological functions in age-associated diseases. One of the major causes of age-related diseases is oxidative stress. In recent years, the importance of H2S has become clear, although its antioxidant function has not yet been fully explored. The enzymes cystathionine ß-synthase, cystathionine γ-lya-se, and 3-mercaptopyruvate sulfurtransferase are involved in the enzymatic production of H2S. Previously, H2S was considered a neuromodulator, given its role in long-term hippocampal potentiation, but it is now also recognized as an antioxidant in age-related neurodegeneration. Due to aerobic metabolism, the central nervous system is vulnerable to oxidative stress in brain aging, resulting in age-associated degenerative diseases. H2S exerts its antioxidant effect by limiting free radical reactions through the activation of antioxidant enzymes, including superoxide dismutase, catalase, and glutathione peroxidase, which protect against the effects of aging by regulating apoptosis-related genes, including p53, Bax, and Bcl-2. This review explores the implications and mechanisms of H2S as an antioxidant in age-associated neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease, and Down syndrome.

Potential for therapeutic use of hydrogen sulfide in oxidative stress-induced neurodegenerative diseases.

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-ß (Aß) 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.

Big data differential analysis of microglial cell responses in neurodegenerative diseases.

Microarray technology has become an indispensable tool for monitoring the levels of gene expression in a given organism through organization, analysis, interpretation, and utilization of biological sequences. Importantly, preliminary microarray gene expression differs from experimentally validated gene expression. Generally, microarray analysis of gene expression in microglial cells is used to identify genes in the brain and spinal cord that are responsible for the onset of neurodegenerative diseases; these genes are either upregulated or downregulated. In the present study, 770 genes identified in prior publications, including experimental studies, were analyzed to determine whether these genes encode novel disease genes. Among the genes published, 340 genes were matched among multiple publications, whereas 430 genes were mismatched; the matched genes were presumed to have the greatest likelihood of contributing to neurodegenerative diseases and thus to be potentially useful target genes for treatment of neurodegenerative diseases. In protein and mRNA expression studies, matched and mismatched genes showed 99% and 97% potentiality, respectively. In addition, some genes identified in microarray analyses were significantly different from those in experimentally validated expression patterns. This study identified novel genes in microglial cells through comparative analysis of published microarray and experimental data on neurodegenerative diseases.