Hydrogen Sulfide (H 2 S) Signaling as a Protective Mechanism against Endogenous and Exogenous Neurotoxicants.

Autor: Aschner M; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Skalny AV; World-Class Research Center 'Digital Biodesign and Personalized Healthcare', IM Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia.; Institute of Bioelementology, Orenburg State University, 460000 Orenburg, Russia., Ke T; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., da Rocha JB; Departamento de Bioquímica e Biologia Molecular, CCNE, Universidade Federal de Santa Maria, Santa Maria, RS, Brazil., Paoliello MM; Department of Molecular Pharmacology, Albert Einstein College of Medicine, Bronx, NY 10461, USA., Santamaria A; Laboratorio de Aminoácidos Excitadores/Laboratorio de Neurofarmacología Molecular y Nanotecnología, Instituto Nacional de Neurología y Neurocirugía, Mexico City 14269, Mexico., Bornhorst J; Food Chemistry, Faculty of Mathematics and Natural Sciences, University of Wuppertal, Wuppertal, Germany.; TraceAge - DFG Research Unit on Interactions of Essential Trace Elements in Healthy and Diseased Elderly (FOR 2558), Berlin-Potsdam-Jena- Wuppertal, Germany., Rongzhu L; Department of Preventive Medicine and Public Health Laboratory Science, School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China., Svistunov AA; World-Class Research Center 'Digital Biodesign and Personalized Healthcare', IM Sechenov First Moscow State Medical University (Sechenov University), 119435 Moscow, Russia., Djordevic AB; Department of Toxicology 'Akademik Danilo Soldatović', Faculty of Pharmacy, University of Belgrade, 11000 Belgrade, Serbia., Tinkov AA; Laboratory of Molecular Dietetics, IM Sechenov First Moscow State Medical University, Moscow 119146, Russia.; Institute of Bioelementology, Orenburg State University, 460000 Orenburg, Russia.
Jazyk: angličtina
Zdroj: Current neuropharmacology [Curr Neuropharmacol] 2022; Vol. 20 (10), pp. 1908-1924.
DOI: 10.2174/1570159X20666220302101854
Abstrakt: In view of the significant role of H 2 S in brain functioning, it is proposed that H 2 S may also possess protective effects against adverse effects of neurotoxicants. Therefore, the objective of the present review is to discuss the neuroprotective effects of H 2 S 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 H 2 S 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, H 2 S 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 H 2 S metabolism through the inhibition of H 2 S-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 H 2 S 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 H 2 S-synthetizing enzymes or the use of H 2 S-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.
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Databáze: MEDLINE
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