H<sub>2</sub>S in the neurodegeneration: a "double-faced Janus"
This paper reviews current literature data on the participation of hydrogen sulfide (H<sub>2</sub>S) in the pathogenesis of neurodegenerative disorders - Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD) and amyotrophic lateral sclerosis (ALS). In the CNS the level of H<sub>2</sub>S is determined by the enzymes of its synthesis - cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). H<sub>2</sub>S is a gasotransmitter, the action of which is realized through chemical and conformational modification of protein molecules simultaneously in spacious pools of cells - in a «broad field». The effects of H<sub>2</sub>S are highly divergent when a certain threshold is reached, it moves from the neuroprotection to the neurodegeneration. The neurodegeneration is mediated by both increased (in ALS) and decreased (PD, AD, HD) levels of H<sub>2</sub>S production, which is determined by the activity of different enzymes of its synthesis - CBS (PD, AD, ALS) or CSE (HD) - depending on the specificity of the certain disorder, that leads to the deployment of the especial pattern of neurological events. The disturbances in sulfur-containing amino acids metabolism and thiol-disulfide homeostasis are an integrative part in H<sub>2</sub>S-dependent mechanism of the neurodegeneration. The opposite/divergent negative effect of H<sub>2</sub>S, the involvement of different enzymes of its synthesis and some products of transformation in the pathological process suggest about the dual nature of H<sub>2</sub>S as a signaling molecule at neurodegenerative disorders.