The Role of Hydrogen Sulfide in Regulation of Cell Death following Neurotrauma and Related Neurodegenerative and Psychiatric Diseases

Abstract

Injuries of the central (CNS) and peripheral nervous system (PNS) are a serious problem of the modern healthcare system. The situation is complicated by the lack of clinically effective neuroprotective drugs that can protect damaged neurons and glial cells from death. In addition, people who have undergone neurotrauma often develop mental disorders and neurodegenerative diseases that worsen the quality of life up to severe disability and death. Hydrogen sulfide (H2S) is a gaseous signaling molecule that performs various cellular functions in normal and pathological conditions. However, the role of H2S in neurotrauma and mental disorders remains unexplored and sometimes controversial. In this large-scale review study, we examined the various biological effects of H2S associated with survival and cell death in trauma to the brain, spinal cord, and PNS, and the signaling mechanisms underlying the pathogenesis of mental illnesses, such as cognitive impairment, encephalopathy, depression and anxiety disorders, epilepsy and chronic pain. We also studied the role of H2S in the pathogenesis of neurodegenerative diseases: Alzheimer’s disease (AD) and Parkinson’s disease (PD). In addition, we reviewed the current state of the art study of H2S donors as neuroprotectors and the possibility of their therapeutic uses in medicine. Our study showed that H2S has great neuroprotective potential. H2S reduces oxidative stress, lipid peroxidation, and neuroinflammation; inhibits processes associated with apoptosis, autophagy, ferroptosis and pyroptosis; prevents the destruction of the blood-brain barrier; increases the expression of neurotrophic factors; and models the activity of Ca2+ channels in neurotrauma. In addition, H2S activates neuroprotective signaling pathways in psychiatric and neurodegenerative diseases. However, high levels of H2S can cause cytotoxic effects. Thus, the development of H2S-associated neuroprotectors seems to be especially relevant. However, so far, all H2S modulators are at the stage of preclinical trials. Nevertheless, many of them show a high neuroprotective effect in various animal models of neurotrauma and related disorders. Despite the fact that our review is very extensive and detailed, it is well structured right down to the conclusions, which will allow researchers to quickly find the proper information they are interested in.

Hydrogen Sulfide: An Emerging Regulator of Oxidative Stress and Cellular Homeostasis—A Comprehensive One-Year Review

“…H 2 S’s multifaceted role in modulating lipid peroxidation and cellular redox balance positions it as a potent inhibitor of ferroptosis. Its capacity to scavenge lipid peroxides and ROS and promote the expression of antioxidant enzymes, such as glutathione peroxidase 4 (GPX4), highlights its regulatory prowess in thwarting ferroptotic processes [ 10 , 41 ].…”

“…It also exerts anti-inflammatory effects by inhibiting NF-κB activation. Additionally, H 2 S displays cytoprotective effects by scavenging ROS and enhancing antioxidant enzyme activities, mitigating oxidative stress and cellular damage [ 10 , 41 ].…”

“…This highlights the importance of ongoing research into the intricate biochemistry of H 2 S and its physiological and pathological roles in health and disease. As a regulator of oxidative stress and cellular homeostasis, H 2 S holds immense therapeutic potential for various conditions [ 41 ].…”

Recent advances in the application of gasotransmitters in spinal cord injury

“…Research has found that H 2 S, similar to CO and NO, plays an important role in anti-inflammatory and anti-apoptotic effects in oxidative stress reactions [ 11 , 12 ]. H 2 S and its donor, sodium hydrosulfide (NaHS), have protective effects on the spinal cord and related diseases [ 13 , 14 ]. H 2 S is also effective in the treatment of SCI-induced complications, such as osteoporosis [ 15 ].…”

The Role of Hydrogen Sulfide in the Localization and Expression of p53 and Cell Death in the Nervous Tissue in Traumatic Brain Injury and Axotomy

“…Typically, in neurotrauma, H 2 S levels tend to decrease, which adversely affects the survival of neurons and glial cells. H 2 S mainly has a neuroprotective effect by reducing oxidative stress, activating antioxidant enzymes, and reducing the level of neuroinflammation and apoptosis [9][10][11]. Of particular interest are the subtle H 2 S-dependent mechanisms of regulation of proapoptotic signaling through direct interaction with target proapoptotic proteins through S-sulfhydration or persulfhydration of cysteine residues, inhibition or activation of various signaling pathways, etc.…”