# Hydrogen Sulfide: A Multitarget Therapeutic for Neuroinflammation in Neurodegenerative Diseases

## TL;DR

This paper reviews how hydrogen sulfide may help treat neurodegenerative diseases by reducing harmful brain inflammation.

## Contribution

The paper highlights H2S as a multitarget therapeutic for neuroinflammation and explores new clinical applications and mechanisms.

## Key findings

- H2S shows anti-inflammatory effects through modulation of glial activity and blood–brain barrier disruption.
- Preclinical data suggest H2S donors have a defined therapeutic window based on dose–exposure–response relationships.
- Spatial multiomics and microbiota-targeted approaches may improve H2S-based treatments.

## Abstract

Neurodegenerative diseases (NDDs) are characterized by the progressive degeneration of specific neuronal populations, remain incurable, and impose an escalating global health burden due to aging populations. While therapeutic options had expanded in recent years, their overall efficacy remained limited. Neuroinflammation emerged as a central factor in the pathogenesis of NDDs. Hydrogen sulfide (H2S), an endogenous gasotransmitter known for its potent anti-inflammatory properties, gained attention as a potential therapeutic agent. This review provided a comprehensive overview of the role of neuroinflammation in NDDs, elucidated the molecular mechanisms through which H2S exerted its anti-inflammatory effects, and discussed recent advancements and potential clinical applications. Special emphasis was placed on the modulation of glial activity, disruption of the blood–brain barrier, regulation of the gut–brain axis, and the interplay between mitochondria and inflammasomes. Furthermore, the review integrated preclinical data on dose–exposure–response relationships to define the therapeutic window of various H2S donors. It also explored the potential of spatial multiomics and microbiota-targeted approaches to facilitate more precise H2S-based interventions. These insights provide important scientific merit for elucidating the mechanisms of NDDs and hold urgent practical relevance for developing novel therapeutics to mitigate disease progression.