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

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 (H 2 S). They all have similar functions: relaxing blood vessels, smoothing muscles, and getting involved in the regulation of neuronal excitation, learning, and memory. The cystathionine b-synthase (CBS), 3-mercaptopyruvate sulfur transferase acts together with cysteine aminotransferase (3-MST/CAT), cystathionine g-lyase (CSE), and 3-mercaptopyruvate sulfur transferase with D-amino acid oxidase (3-MST/DAO) pathways are involved in the enzymatic production of H 2 S. More and more researches focus on the role of H 2 S in the central nervous system (CNS), and H 2 S 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. H 2 S 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 H 2 S 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.

Hydrogen sulfide action in the regulation of plant autophagy

“…Although the role of H 2 S that regulates ER-phagy needs to be further studied, quite recent publications have described the beneficial effect of H 2 S inhibiting ER stress, improving cellular bioenergetics and preventing autophagic arrest [70]. Therefore, it has been shown the beneficial effect of sulfide alleviating various diseases, such as central nervous system degenerative diseases [71] and disruption of the blood-spinal cord barrier [72]. Unfortunately, studies on the role of H 2 S in the regulation of ER-phagy in plants are scarce.…”

The Mitochondrial Carnitine Acyl-carnitine Carrier (SLC25A20): Molecular Mechanisms of Transport, Role in Redox Sensing and Interaction with Drugs

“…Beyond the previously described signals acting on CAC, it has been demonstrated that CAC is an H 2 S sensor. H 2 S is one of the endogenous gas transmitters (NO, CO and H 2 S), which is produced by several enzymatic pathways, two of them being mitochondrial [ 125 , 126 , 127 , 128 , 129 ]. H 2 S exerts its action on CAC interacting with the “crucial” Cys-136 and Cys-155 couple.…”

H2S Donors and Their Use in Medicinal Chemistry

“…H 2 S regulates ERS and shows a broad variety of cytoprotective and physiological functions in CNS degenerative diseases. The neuroprotective effect of H 2 S for ERS has an important role in various CNS diseases as well as Parkinson’s disease, depression disorders, and Alzheimer’s disease [ 98 ].…”

“…H 2 S donors, then, could represent a potential therapeutic opportunity for the treatment of COVID-19 [ 103 ]. The alteration of H 2 S levels in COVID-19 represent further evidence of the need to regulate the homeostasis of this gasotransmitter, considering that the alteration of H 2 S levels has an important role in several diseases [ 89 , 90 , 91 , 92 , 93 , 94 , 95 , 96 , 97 , 98 , 99 , 100 , 101 , 102 , 103 , 104 ].…”