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

Amir H. Sharif, Mohammed Iqbal, Bahareh Manhoosh, Negin Gholampoor, Dan Ma, Mandeep Marwah, Lissette Sanchez-Aranguren*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


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.
Original languageEnglish
Pages (from-to)1981-1996
JournalNeurochemical Research
Issue number7
Early online date10 Feb 2023
Publication statusPublished - Jul 2023

Bibliographical note

Copyright © The Author(s), 2023. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit https://creativecommons.org/licenses/by/4.0/.

Funding: This work was supported by the Royal Society Grant - Round 1 2021 (RGS\R1\221169) and by the Sir Halley Stewart Trust (Ref number 2728). The views expressed within this report are those of the authors and not necessarily those of the Trust, both awarded to LSA.


  • Central nervous system
  • Hydrogen sulphide
  • Hydrogen sulphide-donating compounds


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