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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 (H<jats:sub>2<\/jats:sub>S) 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. H<jats:sub>2<\/jats:sub>S, produced by endogenous sources, is maintained at low levels in the CNS. However, defects in the biosynthetic and catabolic routes for H<jats:sub>2<\/jats:sub>S metabolism have been identified in CNS-related disorders. Approaches to restore H<jats:sub>2<\/jats:sub>S availability using H<jats:sub>2<\/jats:sub>S-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 H<jats:sub>2<\/jats:sub>S delivery, dosage regimes and feasibility to successfully target CNS tissues. Here, we highlight the molecular mechanisms of H<jats:sub>2<\/jats:sub>S-dependent restoration of neurological functions in different models of CNS disease whilst summarising current administration approaches for these H<jats:sub>2<\/jats:sub>S-based compounds. We also address existing barriers in H<jats:sub>2<\/jats:sub>S donor delivery by showcasing current advances in mediating these constrains through novel biomaterial-based carriers for H<jats:sub>2<\/jats:sub>S donors.<\/jats:p>","DOI":"10.1007\/s11064-023-03887-y","type":"journal-article","created":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T00:35:35Z","timestamp":1676075735000},"page":"1981-1996","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":49,"title":["Hydrogen Sulphide-Based Therapeutics for Neurological Conditions: Perspectives and Challenges"],"prefix":"10.1007","volume":"48","author":[{"given":"Amir H.","family":"Sharif","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed","family":"Iqbal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bahareh","family":"Manhoosh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Negin","family":"Gholampoor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mandeep","family":"Marwah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4663-5752","authenticated-orcid":false,"given":"Lissette","family":"Sanchez-Aranguren","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2023,2,10]]},"reference":[{"issue":"5","key":"3887_CR1","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1016\/S1474-4422(18)30499-X","volume":"18","author":"VL Feigin","year":"2019","unstructured":"Feigin VL, Nichols E, Alam T, Bannick MS, Beghi E, Blake N, Culpepper WJ, Dorsey ER, Elbaz A, Ellenbogen RG, Fisher JL (2019) Global, regional, and national burden of neurological disorders, 1990\u20132016:a systematic analysis for the Global Burden of Disease Study 2016. 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