Hydrogen Sulfide Signaling in Neurodegenerative Movement Disorders

Hydrogen sulfide (H₂S) is a gaseous signaling molecule, also known as a gasotransmitter, present in nearly all mammalian organs. It plays crucial roles in regulating various physiological processes in both the brain and peripheral systems. The body maintains tight control over H₂S levels, as both excessive and deficient levels can disrupt normal physiological functions and lead to disease. H₂S has a significant impact on cognitive and motor functions, which are often compromised in neurodegenerative disorders. It modulates signaling and metabolism primarily by post-translationally modifying reactive cysteine residues on proteins through sulfhydration, also known as persulfidation. This chapter reviews the signaling mechanisms regulated by H₂S in neurodegenerative diseases that significantly affect motor function, specifically focusing on Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), spinocerebellar ataxia (SCA), and Leigh syndrome (LS), as well as other mitochondrial disorders. While PD, HD, and SCA are linked to decreased levels of H₂S, elevated levels of H₂S are associated with ALS, DS, and LS. We also explore potential therapeutic applications of modulating H₂S levels in the brain.