H2S IN THE NEURODEGENERATION: A "DOUBLE-FACED JANUS"
Evgeniya Eduardovna KOLESNIKOVA
A.O. Kovalevsky Institute of Marine Biological Research of RAS
Keywords: сульфид водорода, нейродегенерация, болезнь Паркинсона, болезнь Альцгеймера, болезнь Хантингтона, боковой амиотрофический склероз, hydrogen sulfide, neurodegeneration, Parkinson’s disease, Alzheimer’s disease, Huntington’s disease, amyotrophic lateral sclerosis
Abstract
This paper reviews current literature data on the participation of hydrogen sulfide (H2S)
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 H2S is determined by the enzymes of its synthesis - cystathionine-β-synthase (CBS) and cystathionine-γ-lyase (CSE). H2S
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 H2S
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
H2S 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 H2S-dependent mechanism of the neurodegeneration. The opposite/divergent negative effect of H2S,
the involvement of different enzymes of its synthesis and some products
of transformation in the pathological process suggest about the dual
nature of H2S as a signaling molecule at neurodegenerative disorders.
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