Table 2.

Data regarding Hydrogen Sulfide and Histone Modifications in Neurodegenerative Diseases.

Ref.	Title	Pathology	Extracted Data Regarding Epigenetics	Major Outcome
[45]	Hydrogen sulfide-induced post-translational modification as a potential drug target	Neurodegenerative disease, Alzheimer’s, Parkinson’s, Huntington’s diseases	H2S affects histones. S-sulfhydration of histones can regulate gene expression and epigenetic modifications. H2S-mediated S-sulfhydration of histone modifiers, such as Sirt1, affects aging, metabolism, and oxidative stress tolerance.	H2S-S-sulfhydration histone modifiers, such as Sirt1, influences aging, metabolism, and oxidative stress.
[84]	Exploring mitochondrial hydrogen sulfide signalling for therapeutic interventions in vascular diseases	Neurodegenerative diseases, Parkinson’s disease	H2S administration has been found to increase antioxidant proteins such as Trx-1 through the Nrf-2 pathway, leading to cardioprotection in ischemia-induced heart failure. H2S also regulates members of the SIRT family, such as SIRT1, SIRT3, and SIRT6, which play critical roles in histone and non-histone protein modifications. These findings highlight the importance of H2S-SIRT interactions in mediating cellular protection and physiological effects.	H2S-SIRT interactions mediate cellular protection, impacting histone modifications and cellular functions.
[149]	Hydrogen Sulfide Biology and Its Role in Cancer	Neurodegenerative diseases	H2S can increase E-cadherin levels, inhibit histone deacetylase, and modulate NF-κB signaling, resulting in anti-metastatic and tumor-suppressive effects. However, the exact molecular targets underlying H2S’s diverse effects on biological processes, including cancer, require further investigation. Chronic exposure to H2S or its derivatives may have detrimental effects, including NF-κB inhibition and apoptosis.	H2S influences histone deacetylase and acetyltransferase activities, impacting gene expression and chromatin structure.
[150]	Protective effect of hydrogen sulfide is mediated by negative regulation of epigenetic histone acetylation in Parkinson’s disease	Neurodegenerative diseases Parkinson’s disease	Histone modifications and DNA methylation have been linked to the pathogenicity of Parkinson’s disease (PD). Histone deacetylase (HDAC) enzymes mediate chromatin condensation and inhibit gene transcription, while histone acetyltransferases (HAT) reverse these effects. Imbalances in HDAC and HAT activities are associated with neurodegenerative diseases, including PD. Inhibiting HDAC has shown promise in rescuing cells from degeneration in PD models. This study investigated the impact of HDAC inhibitor TSA on 6-hydroxydopamine-induced neurotoxicity in PD animal models.	H2S negatively regulates histone acetylation, impacting gene expression and neuronal survival in PD.
[151]	One-carbon epigenetics and redox biology of neurodegeneration	Alzheimer’s disease Parkinson’s disease Amyotrophic lateral sclerosis	Histone proteins form the histone octamer around which DNA is wrapped to create nucleosomes. Post-translational modifications (PTMs) of histone tails, including acetylation and methylation, regulate chromatin structure and gene expression. Histone acetyltransferases (HATs) add acetyl groups to lysine residues, promoting transcription, while histone deacetylases (HDACs) remove acetyl groups, leading to chromatin compaction and transcriptional inhibition.	H2S modulates histone acetyltransferases (HATs) and histone deacetylases (HDACs), influencing gene expression and chromatin remodeling.
[152]	Brain energy rescue: an emerging therapeutic concept for neurodegenerative disorders of ageing	Neurodegenerative disorders	Histones, as crucial chromatin components, are subject to post-translational modifications, including acetylation, which influences gene expression. Hydrogen sulfide (H2S) plays a role in cellular energetics by regulating the availability of acetyl-CoA, a precursor of acetyl groups used in histone acetylation. H2S-related pathways, such as sirtuin 1 activation, mitochondrial function, and gut microbiota-produced short-chain fatty acids, also impact histone modifications, linking cellular energetics to epigenetic regulation. Targeting these mechanisms may hold therapeutic potential for neurodegenerative disorders.	H2S-related pathways influence histone modifications, linking cellular energetics to epigenetic regulation in neurodegenerative disorders.