Effect of hydrogen sulfide on alpha-synuclein aggregation and cell viability

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• Parkinson's disease (PD) involves α-synuclein (α-Syn) aggregation and Lewy body formation.
• Familial PD mutations in α-Syn are linked to increased neuronal toxicity.
• Inhibiting α-Syn aggregation is a crucial therapeutic target.

Purpose of the Study:

• To investigate the potential of hydrogen sulfide (H2S) donor, sodium hydrosulfide (NaHS), in inhibiting α-Syn aggregation.
• To examine the conformation-specific effects of NaHS on wild-type (wt) and mutant α-Syn.

Main Methods:

• Assessed NaHS effects on α-Syn fibril growth kinetics and structural changes in vitro.
• Utilized self-seeding and cross-seeding assays with wt and familial PD mutant α-Syn (A53T).
• Evaluated NaHS impact on α-Syn oligomer formation and cell viability in an α-Syn overexpressing cell model.

Main Results:

• NaHS significantly slowed self- and cross-seeded A53T α-Syn fibril formation, but not wt α-Syn.
• Observed reduced fibril length in vitro and decreased oligomer number and filament length in cells.
• NaHS treatment rescued the viability of A53T α-Syn overexpressing cells seeded with preformed fibrils.

Conclusions:

• Hydrogen sulfide exhibits a conformation-specific inhibitory effect on α-Syn aggregation.
• NaHS demonstrates potential therapeutic benefits by reducing toxic α-Syn aggregates and enhancing cell survival.
• Further research into H2S for PD treatment is warranted.