Hydrogen Sulphide-Based Therapeutics for Neurological Conditions: Perspectives and Challenges

Abstract

Central nervous system (CNS)-related conditions are currently the leading cause of disability worldwide, posing a significant burden to health systems, individuals and their families. Although the molecular mechanisms implicated in these disorders may be varied, neurological conditions have been increasingly associated with inflammation and/or impaired oxidative response leading to further neural cell damages. Therefore, therapeutic approaches targeting these defective molecular mechanisms have been vastly explored. Hydrogen sulphide (H2S) has emerged as a modulator of both inflammation and oxidative stress with a neuroprotective role, therefore, has gained interest in the treatment of neurological disorders. H2S, produced by endogenous sources, is maintained at low levels in the CNS. However, defects in the biosynthetic and catabolic routes for H2S metabolism have been identified in CNS-related disorders. Approaches to restore H2S availability using H2S-donating compounds have been recently explored in many models of neurological conditions. Nonetheless, we still need to elucidate the potential for these compounds not only to ameliorate defective biological routes, but also to better comprehend the implications on H2S delivery, dosage regimes and feasibility to successfully target CNS tissues. Here, we highlight the molecular mechanisms of H2S-dependent restoration of neurological functions in different models of CNS disease whilst summarising current administration approaches for these H2S-based compounds. We also address existing barriers in H2S donor delivery by showcasing current advances in mediating these constrains through novel biomaterial-based carriers for H2S donors.

The Role of Hydrogen Sulfide (H2S) in Epigenetic Regulation of Neurodegenerative Diseases: A Systematic Review

“…H 2 S has been found to influence neuroinflammation, oxidative stress, and mitochondrial dysfunction, all of which are implicated in the pathogenesis of neurodegenerative disorders. Its significance in neurodegeneration is an intriguing area of investigation, with the potential to reveal new therapeutic strategies [ 54 , 83 , 84 ]. By contextualizing the study of H 2 S within the framework of evolution and epigenetics, we obtain a deeper understanding of its complex physio-pathology [ 45 , 85 , 86 , 87 ].…”

“…Moreover, H 2 S can affect mitochondrial function and induce oxidative stress, both associated with dopaminergic neuronal death in PD [ 101 , 102 , 103 ]. H 2 S-induced inflammation and microglial activation may also affect disease pathogenesis [ 83 , 103 , 104 ].…”

Chemistry of Hydrogen Sulfide—Pathological and Physiological Functions in Mammalian Cells

“…In addition, H 2 S exerts its action on important functions of the central nervous system and provides neuroprotective protection against oxidative stress. There is a belief that it has potentially protective properties against neurodegenerative diseases such as Parkinson's disease, Alzheimer's disease and Huntington's disease [106]; spinocerebellar ataxia; and traumatic brain injury. It has been published that H 2 S levels are reduced in the brains of patients with Alzheimer's disease compared to healthy individuals [107].…”

Dietary glucosinolates derived isothiocyanates: chemical properties, metabolism and their potential in prevention of Alzheimer’s disease

“…ITCs significantly decrease NF-kβ translocation with the inhibition of proinflammatory cytokines ( Latronico et al, 2021 ). Hydrogen sulphide (H 2 S) is another important signal molecule in CNS; it could represent an intriguing strategy for the treatment of neurodegenerative diseases ( Tabassum and Jeong, 2019 ; Sharif et al, 2023 ). Beside this, it also play a key role in many aspects of human health like in antiproliferation, cardioprotection, chemoprevention, etc.…”