Dimerization propensities of Synucleins are not predictive for Synuclein aggregation.

Area of Science:

• Neuroscience
• Molecular Biology
• Biochemistry

Background:

• Alpha-Synuclein (αS) aggregation is a key feature of Parkinson's disease and other synucleinopathies.
• The precise mechanisms driving αS aggregation and fibril formation remain largely unknown.
• Differences in aggregation propensity among αS, βS, and γS suggest distinct roles in neurological disorders.

Purpose of the Study:

• To investigate the initial step of Synuclein aggregation: dimer or oligomer formation.
• To compare the interaction capabilities of αS, βS, and γS in a cellular context.
• To determine if early-stage Synuclein interactions predict later aggregation behavior.

Main Methods:

• Utilized Bimolecular Fluorescence Complementation (BiFC) in cells to study Synuclein interactions.
• Assessed Synuclein dimerization and oligomerization.
• Acknowledged and addressed limitations of the BiFC assay for Synuclein studies.

Main Results:

• Demonstrated that all three Synucleins (αS, βS, γS) interact with each other similarly.
• Observed limitations in the single-cell BiFC assay's performance for Synucleins.
• Found that Synuclein dimer formation is not indicative of their subsequent aggregation patterns.

Conclusions:

• Synuclein dimerization occurs similarly for αS, βS, and γS.
• Early-stage Synuclein interactions do not correlate with their known divergent aggregation properties.
• Dimerization is not a reliable predictor for Synuclein aggregation in the brain, impacting our understanding of synucleinopathies.