Hydrogen Sulfide and Endoplasmic Reticulum Stress: A Potential Therapeutic Target for Central Nervous System Degeneration Diseases.

Huimin Zhong,Yisheng Zhong,Jun Sun,Lei Guo,Huan Yu,Junjue Chen,Ping Huang

doi:10.3389/fphar.2020.00702

Abstract

There are three members of the endogenous gas transmitter family. The first two are nitric oxide and carbon monoxide, and the third newly added member is hydrogen sulfide (H2S). They all have similar functions: relaxing blood vessels, smoothing muscles, and getting involved in the regulation of neuronal excitation, learning, and memory. The cystathionine β-synthase (CBS), 3-mercaptopyruvate sulfur transferase acts together with cysteine aminotransferase (3-MST/CAT), cystathionine γ-lyase (CSE), and 3-mercaptopyruvate sulfur transferase with D-amino acid oxidase (3-MST/DAO) pathways are involved in the enzymatic production of H2S. More and more researches focus on the role of H2S in the central nervous system (CNS), and H2S plays a significant function in neuroprotection processes, regulating the function of the nervous system as a signaling molecule in the CNS. Endoplasmic reticulum stress (ERS) and protein misfolding in its mechanism are related to neurodegenerative diseases. H2S exhibits a wide variety of cytoprotective and physiological functions in the CNS degenerative diseases by regulating ERS. This review summarized on the neuroprotective effect of H2S for ERS played in several CNS diseases including Alzheimer’s disease, Parkinson’s disease, and depression disorder, and discussed the corresponding possible signaling pathways or mechanisms as well.

Highlights

Hydrogen sulfide (H2S) plays an important role in terms of cell signal transduction and modulation in the central nerve system (CNS), the cardiovascular system, and many organs like hepatic function (Olas, 2015; Wu et al, 2019)
Different studies have recognized that H2S plays an important role in physiological and pathological conditions in the body
Free exogenous H2S is able to exert a physiologic function in neurotransmission and cell survival

Summary

INTRODUCTION

Hydrogen sulfide (H2S) plays an important role in terms of cell signal transduction and modulation in the central nerve system (CNS), the cardiovascular system, and many organs like hepatic function (Olas, 2015; Wu et al, 2019). Activation of astrocytes and microglia inflammatory pathways in neuronal cells will reduce CBS expression, leading to downgrade H2S levels in the brain (Schicho et al, 2006; Kimura et al, 2010). In the presence of high concentrations of DHLA, H2S can be produced from both 3MP and thiosulfate They concluded that DHLA was detected to release H2S effectively from the brain post-nuclear supernatant containing bound sulfane sulfur (Mikami et al, 2011a). Because 3-MST cell expression mutation lacks H2S-producing activity, the concentration of bound sulfur is low (Shibuya et al, 2009b). The increase of extracellular potassium ion concentration causes the intracellular pH of astrocytes to increase to release H2S from the bound sulfur (Ishigami et al, 2009) Another substrate for CAT, aspartate can combine competitively with CAT to suppress the production of H2S. It should be focused on uncovering the exact role and function of H2S in the CNS with the aims of dissecting the involved signaling pathways

ERS OF NEURONS IN CNS

Findings

CONCLUSION AND PERSPECTIVES