Gallic acid interacts with α-synuclein to prevent the structural collapse necessary for its aggregation

Area of Science:

• Biochemistry
• Neuroscience
• Pharmacology

Background:

• Parkinson's disease (PD) is characterized by protein aggregates, primarily amyloid fibrils of α-synuclein.
• Developing inhibitors of amyloid fibril formation or disaggregators is a key therapeutic strategy for PD.

Purpose of the Study:

• To investigate the effect of gallic acid (GA) on α-synuclein amyloid fibril formation.
• To elucidate the mechanism by which GA interacts with α-synuclein.

Main Methods:

• In vitro Thioflavin T fluorescence assays.
• Transmission electron microscopy (TEM).
• Ion mobility-mass spectrometry (IM-MS).
• Nuclear magnetic resonance (NMR) spectroscopy.

Main Results:

• Gallic acid (GA) potently inhibited the in vitro formation of α-synuclein amyloid fibrils.
• GA was shown to stabilize the native structure of α-synuclein.
• NMR spectroscopy indicated a transient interaction between GA and α-synuclein.

Conclusions:

• Gallic acid demonstrates significant potential as an inhibitor of α-synuclein amyloidogenesis.
• GA's mechanism involves stabilizing the native protein structure, preventing aggregation.
• These findings suggest GA as a promising therapeutic candidate for Parkinson's disease.