S-Propargyl-Cysteine Attenuates Stroke Heterogeneity via Promoting Protective Autophagy Across Multiple Neural Cell...

Area of Science:

• Neuroscience
• Biochemistry
• Molecular Biology

Background:

• Ischemic stroke is a leading cause of death and disability globally, with limited effective treatments.
• Hydrogen sulfide (H2S) shows neuroprotective potential, but its role in stroke is debated.
• S-propargyl-cysteine (SPRC), an H2S donor, may offer neuroprotection, but its mechanisms require further elucidation.

Purpose of the Study:

• Investigate the neuroprotective effects of SPRC in ischemic stroke.
• Elucidate the underlying mechanisms, focusing on the interplay between H2S and autophagy.
• Determine if SPRC's effects are dependent on classical H2S-synthesizing enzymes.

Main Methods:

• Single-cell RNA sequencing of ischemic brain tissue to analyze H2S and autophagy gene expression.
• Utilized GEO dataset GSE174574 with Harmony R for batch correction.
• Assessed SPRC's pharmacodynamics and neuroprotection in a rat cerebral ischemia-reperfusion (I/R) model.
• Evaluated SPRC's effects in CBS and 3-MST knockout mice.

Main Results:

• Stroke induced dysregulation of H2S and autophagy genes, particularly in neurons.
• SPRC administration improved neurological function, reduced infarct size, and ameliorated brain injury in rats.
• SPRC provided neuroprotection independently of CBS and 3-MST, preserving endogenous H2S levels.
• SPRC significantly upregulated protective autophagy.

Conclusions:

• SPRC demonstrates neuroprotection in cerebral I/R injury via a CBS/3-MST-independent pathway.
• SPRC-mediated neuroprotection may involve the promotion of protective autophagy.
• SPRC is a potential therapeutic candidate for ischemic stroke, offering neuroprotection and modulating autophagy.