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

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.