Cargando…
Hydrogen Sulfide (H(2)S) Signaling as a Protective Mechanism against Endogenous and Exogenous Neurotoxicants
In view of the significant role of H(2)S 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 H(2)S against toxicity of a wide spectrum...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Bentham Science Publishers
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886801/ https://www.ncbi.nlm.nih.gov/pubmed/35236265 http://dx.doi.org/10.2174/1570159X20666220302101854 |
_version_ | 1784880197135237120 |
---|---|
author | Aschner, Michael Skalny, Anatoly V. Ke, Tao da Rocha, Joao BT Paoliello, Monica MB Santamaria, Abel Bornhorst, Julia Rongzhu, Lu Svistunov, Andrey A. Djordevic, Aleksandra B. Tinkov, Alexey A. |
author_facet | Aschner, Michael Skalny, Anatoly V. Ke, Tao da Rocha, Joao BT Paoliello, Monica MB Santamaria, Abel Bornhorst, Julia Rongzhu, Lu Svistunov, Andrey A. Djordevic, Aleksandra B. Tinkov, Alexey A. |
author_sort | Aschner, Michael |
collection | PubMed |
description | In view of the significant role of H(2)S 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 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, 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 H(2)S 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 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 H2S-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. |
format | Online Article Text |
id | pubmed-9886801 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Bentham Science Publishers |
record_format | MEDLINE/PubMed |
spelling | pubmed-98868012023-02-28 Hydrogen Sulfide (H(2)S) Signaling as a Protective Mechanism against Endogenous and Exogenous Neurotoxicants Aschner, Michael Skalny, Anatoly V. Ke, Tao da Rocha, Joao BT Paoliello, Monica MB Santamaria, Abel Bornhorst, Julia Rongzhu, Lu Svistunov, Andrey A. Djordevic, Aleksandra B. Tinkov, Alexey A. Curr Neuropharmacol Neurology In view of the significant role of H(2)S 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 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, 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 H(2)S 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 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 H2S-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. Bentham Science Publishers 2022-08-31 2022-08-31 /pmc/articles/PMC9886801/ /pubmed/35236265 http://dx.doi.org/10.2174/1570159X20666220302101854 Text en © 2022 Bentham Science Publishers https://creativecommons.org/licenses/by-nc/4.0/ This is an open access article licensed under the terms of the Creative Commons Attribution-Non-Commercial 4.0 International Public License (CC BY-NC 4.0) (https://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited. |
spellingShingle | Neurology Aschner, Michael Skalny, Anatoly V. Ke, Tao da Rocha, Joao BT Paoliello, Monica MB Santamaria, Abel Bornhorst, Julia Rongzhu, Lu Svistunov, Andrey A. Djordevic, Aleksandra B. Tinkov, Alexey A. Hydrogen Sulfide (H(2)S) Signaling as a Protective Mechanism against Endogenous and Exogenous Neurotoxicants |
title | Hydrogen Sulfide (H(2)S) Signaling as a Protective Mechanism against Endogenous and Exogenous Neurotoxicants |
title_full | Hydrogen Sulfide (H(2)S) Signaling as a Protective Mechanism against Endogenous and Exogenous Neurotoxicants |
title_fullStr | Hydrogen Sulfide (H(2)S) Signaling as a Protective Mechanism against Endogenous and Exogenous Neurotoxicants |
title_full_unstemmed | Hydrogen Sulfide (H(2)S) Signaling as a Protective Mechanism against Endogenous and Exogenous Neurotoxicants |
title_short | Hydrogen Sulfide (H(2)S) Signaling as a Protective Mechanism against Endogenous and Exogenous Neurotoxicants |
title_sort | hydrogen sulfide (h(2)s) signaling as a protective mechanism against endogenous and exogenous neurotoxicants |
topic | Neurology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886801/ https://www.ncbi.nlm.nih.gov/pubmed/35236265 http://dx.doi.org/10.2174/1570159X20666220302101854 |
work_keys_str_mv | AT aschnermichael hydrogensulfideh2ssignalingasaprotectivemechanismagainstendogenousandexogenousneurotoxicants AT skalnyanatolyv hydrogensulfideh2ssignalingasaprotectivemechanismagainstendogenousandexogenousneurotoxicants AT ketao hydrogensulfideh2ssignalingasaprotectivemechanismagainstendogenousandexogenousneurotoxicants AT darochajoaobt hydrogensulfideh2ssignalingasaprotectivemechanismagainstendogenousandexogenousneurotoxicants AT paoliellomonicamb hydrogensulfideh2ssignalingasaprotectivemechanismagainstendogenousandexogenousneurotoxicants AT santamariaabel hydrogensulfideh2ssignalingasaprotectivemechanismagainstendogenousandexogenousneurotoxicants AT bornhorstjulia hydrogensulfideh2ssignalingasaprotectivemechanismagainstendogenousandexogenousneurotoxicants AT rongzhulu hydrogensulfideh2ssignalingasaprotectivemechanismagainstendogenousandexogenousneurotoxicants AT svistunovandreya hydrogensulfideh2ssignalingasaprotectivemechanismagainstendogenousandexogenousneurotoxicants AT djordevicaleksandrab hydrogensulfideh2ssignalingasaprotectivemechanismagainstendogenousandexogenousneurotoxicants AT tinkovalexeya hydrogensulfideh2ssignalingasaprotectivemechanismagainstendogenousandexogenousneurotoxicants |