Mechanistic Intimate Insights into the Role of Hydrogen Sulfide in Alzheimer's Disease: A Recent Systematic Review

Abstract

In the rapidly evolving field of Alzheimer's Disease (AD) research, the intricate role of Hydrogen Sulfide (H₂S) has garnered critical attention for its diverse involvement in both pathological substrates and prospective therapeutic paradigms. While conventional pathophysiological models of AD have primarily emphasized the significance of amyloid-beta (Aβ) deposition and tau protein hyperphosphorylation, this targeted systematic review meticulously aggregates and rigorously appraises seminal contributions from the past year elucidating the complex mechanisms of H₂S in AD pathogenesis. Current scholarly literature accentuates H₂S's dual role, delineating its regulatory functions in critical cellular processes-such as neurotransmission, inflammation, and oxidative stress homeostasis-while concurrently highlighting its disruptive impact on quintessential AD biomarkers. Moreover, this review illuminates the nuanced mechanistic intimate interactions of H₂S in cerebrovascular and cardiovascular pathology associated with AD, thereby exploring avant-garde therapeutic modalities, including sulfurous mineral water inhalations and mud therapy. By emphasizing the potential for therapeutic modulation of H₂S via both donors and inhibitors, this review accentuates the imperative for future research endeavors to deepen our understanding, thereby potentially advancing novel diagnostic and therapeutic strategies in AD.

Keywords: Alzheimer’s Disease; Hydrogen Sulfide (H2S); amyloid-beta (Aβ) aggregation; cellular homeostasis; neuroinflammation; neuroprotection; tau hyperphosphorylation.

Figure 1

Multifaceted roles of H₂S in Alzheimer’s Disease. 1. Biphasic, concentration-dependent effects of H₂S, emphasizing its dual role as a toxicant at high concentrations and a cellular signaling molecule at low concentrations. 2. H₂S’s involvement in redox homeostasis, emphasizing its protective role in mitochondrial function and regulation of oxidative stress. 3. Putative role of H₂S in promoting the clearance of amyloid-beta (Aβ) peptides. 4. Involvement of H₂S in modulating inflammatory pathways.