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

Abstract

This review explores the emerging role of hydrogen sulfide (H₂S) in modulating epigenetic mechanisms involved in neurodegenerative diseases. Accumulating evidence has begun to elucidate the multifaceted ways in which H₂S influences the epigenetic landscape and, subsequently, the progression of various neurodegenerative disorders, including Alzheimer's, Parkinson's, and Huntington's disease. H₂S can modulate key components of the epigenetic machinery, such as DNA methylation, histone modifications, and non-coding RNAs, impacting gene expression and cellular functions relevant to neuronal survival, inflammation, and synaptic plasticity. We synthesize recent research that positions H₂S as an essential player within this intricate network, with the potential to open new therapeutic avenues for these currently incurable conditions. Despite significant progress, there remains a considerable gap in our understanding of the precise molecular mechanisms and the potential therapeutic implications of modulating H₂S levels or its downstream targets. We conclude by identifying future directions for research aimed at exploiting the therapeutic potential of H₂S in neurodegenerative diseases.

Keywords: Alzheimer’s disease; DNA methylation; Huntington’s disease; Parkinson’s disease; epigenetic regulation; histone modifications; hydrogen sulfide; neurodegenerative diseases; non-coding RNAs.

Figure 1

This figure illustrates the central role of Hydrogen Sulfide (H₂S) in epigenetic regulation and its interactions with various processes associated with neurodegenerative diseases. H₂S affects epigenetic mechanisms, including histone modification, DNA methylation, and non-coding RNAs, which modulate gene expression and cellular functions relevant to neurodegeneration. H₂S influences reactive oxygen species (ROS) production and oxidative stress levels, which play a critical role in the pathogenesis of neurodegenerative disorders. By reducing ROS production (blue arrow) and inhibiting ROS-generating processes at the mitochondrial level (red arrows), H₂S impacts a broad spectrum of biological functions, as depicted in this figure for illustrative purposes. The interplay between H₂S, epigenetic processes, and oxidative stress offers valuable insights into the molecular mechanisms underlying neurodegeneration and highlights the potential for therapeutic interventions to restore epigenetic balance and mitigate oxidative stress to combat neurodegenerative diseases effectively. The figure corroborates 3 major parts: 1. external sources and internal production of H₂S; 2. the epigenetic role of H₂S; and 3. the physiological connections presented in a simplified way.

Figure 2

Adapted PRISMA flow diagram, customized for our study.