Hydrogen Sulfide (H2S) Signaling as a Protective Mechanism against Endogenous
and Exogenous Neurotoxicants

Michael      Aschner; Anatoly   V.   Skalny; Tao      Ke; Joao BT      da Rocha; Monica   MB   Paoliello; Abel      Santamaria; Julia      Bornhorst; Lu      Rongzhu; Andrey   A.   Svistunov; Aleksandra   B.   Djordevic; Alexey   A.   Tinkov
doi:10.2174/1570159X20666220302101854
Abstract

In view of the significant role of H₂S in brain functioning, it is proposed that H₂S may also possess protective effects against adverse effects of neurotoxicants. Therefore, the objective of the present review is to discuss the neuroprotective effects of H₂S against toxicity of a wide spectrum of endogenous and exogenous agents involved in the pathogenesis of neurological diseases as etiological factors or key players in disease pathogenesis. Generally, the existing data demonstrate that H₂S possesses neuroprotective effects upon exposure to endogenous (amyloid β, glucose, and advanced-glycation end-products, homocysteine, lipopolysaccharide, and ammonia) and exogenous (alcohol, formaldehyde, acrylonitrile, metals, 6-hydroxydopamine, as well as 1-methyl-4-phenyl- 1,2,3,6- tetrahydropyridine (MPTP) and its metabolite 1-methyl-4-phenyl pyridine ion (MPP)) neurotoxicants. On the one hand, neuroprotective effects are mediated by S-sulfhydration of key regulators of antioxidant (Sirt1, Nrf2) and inflammatory response (NF-κB), resulting in the modulation of the downstream signaling, such as SIRT1/TORC1/CREB/BDNF-TrkB, Nrf2/ARE/HO-1, or other pathways. On the other hand, H₂S appears to possess a direct detoxicative effect by binding endogenous (ROS, AGEs, Aβ) and exogenous (MeHg) neurotoxicants, thus reducing their toxicity. Moreover, the alteration of H₂S metabolism through the inhibition of H₂S-synthetizing enzymes in the brain (CBS, 3-MST) may be considered a significant mechanism of neurotoxicity. Taken together, the existing data indicate that the modulation of cerebral H₂S metabolism may be used as a neuroprotective strategy to counteract neurotoxicity of a wide spectrum of endogenous and exogenous neurotoxicants associated with neurodegeneration (Alzheimer’s and Parkinson’s disease), fetal alcohol syndrome, hepatic encephalopathy, environmental neurotoxicant exposure, etc. In this particular case, modulation of H₂S-synthetizing enzymes or the use of H₂S-releasing drugs should be considered as the potential tools, although the particular efficiency and safety of such interventions are to be addressed in further studies.
Keywords: Hydrogen sulfide, sodium hydrosulfide, alcohol, amyloid, metals, neurotoxicants.
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DOI https://dx.doi.org/10.2174/1570159X20666220302101854	Print ISSN 1570-159X
Publisher Name Bentham Science Publisher	Online ISSN 1875-6190
Current Neuropharmacology

Hydrogen Sulfide (H₂S) Signaling as a Protective Mechanism against Endogenous and Exogenous Neurotoxicants

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Current Neuropharmacology

Hydrogen Sulfide (H2S) Signaling as a Protective Mechanism against Endogenous and Exogenous Neurotoxicants

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Hydrogen Sulfide (H₂S) Signaling as a Protective Mechanism against Endogenous and Exogenous Neurotoxicants
