Myricetin Inhibits α-Synuclein Amyloid Aggregation by Delaying the Liquid-to-Solid Phase Transition

Area of Science:

• Biochemistry
• Neuroscience
• Pharmacology

Background:

• Alpha-synuclein (α-Syn) aggregation is a key pathological feature of Parkinson's disease (PD).
• Liquid-liquid phase separation (LLPS) is implicated in the nucleation and amyloid formation of α-Syn.
• Targeting α-Syn aggregation is a crucial strategy for PD treatment.

Purpose of the Study:

• To investigate the effect of myricetin on α-Syn aggregation under LLPS conditions.
• To explore myricetin's mechanism in modulating α-Syn condensate dynamics and amyloid formation.
• To assess myricetin's potential to inhibit or disassemble α-Syn aggregates.

Main Methods:

• Studied α-Syn aggregation and liquid-liquid phase separation (LLPS) in the presence of myricetin.
• Analyzed the morphology and fraction of α-Syn condensates.
• Measured the dynamics of α-Syn condensates using biophysical techniques.
• Investigated the effect of myricetin on the liquid-to-solid phase transition of α-Syn.
• Assessed the disassembly of preformed α-Syn amyloid aggregates by myricetin.

Main Results:

• Myricetin did not alter the initial morphology or phase-separated fraction of α-Syn.
• Myricetin binding reduced the dynamics of α-Syn condensates.
• Myricetin dose-dependently inhibited α-Syn amyloid aggregation by delaying the liquid-to-solid phase transition.
• Myricetin disassembled preformed α-Syn amyloid aggregates.

Conclusions:

• Myricetin inhibits α-Syn amyloid aggregation within condensates by impeding the liquid-to-solid phase transition.
• Targeting the phase transition of α-Syn condensates is a viable strategy for inhibiting PD-related amyloid formation.
• Myricetin shows therapeutic potential for Parkinson's disease by modulating α-Syn aggregation dynamics.