Morin Interacts with α-Synuclein and Retards Its Fibrillation.

Area of Science:

• Biochemistry and Molecular Biology
• Neuroscience
• Pharmacology

Background:

• Alpha-synuclein (αS) intrinsically disordered protein aggregation is central to Parkinson's disease pathogenesis.
• Understanding αS structural dynamics and fibrillation mechanisms is crucial for developing therapeutic interventions.

Purpose of the Study:

• To investigate the interaction between morin hydrate (MOR) and αS in aqueous solution.
• To determine if MOR can stabilize αS structure and inhibit its aggregation.

Main Methods:

• Utilized intrinsic tyrosine fluorescence spectroscopy to study αS-MOR complex formation and binding affinity.
• Employed circular dichroism spectroscopy to analyze protein conformational changes.
• Applied atomic force microscopy and Thioflavin T fluorescence assays to assess αS aggregation and fibrillation.

Main Results:

• MOR formed a 1:1 complex with αS, exhibiting weak binding affinity (∼4.5 × 10^4 M⁻¹) at room temperature.
• MOR stabilized αS structure, increasing α-helical content and reducing disordered regions.
• MOR significantly retarded αS aggregation and fibrillation, as evidenced by AFM and ThT assays.

Conclusions:

• Morin hydrate's weak but effective interaction stabilizes αS structure through hydrophobic and hydrogen bond interactions.
• MOR inhibits key aggregation steps like hydrophobic zipping, thereby retarding amyloid fibril formation.
• These findings suggest MOR as a potential therapeutic agent for Parkinson's disease and related neurodegenerative disorders.