A Master Regulator of α-Synuclein Aggregation.

Parkinson's disease is associated with aggregation of pathological α-synuclein (αSyn) proteins. The central hydrophobic region of αSyn, called NAC, encodes the segment that is crucial and sufficient for the toxic aggregation of αSyn. However, if any other region, including the NAC flanking region, modulates αSyn, aggregation is still unknown. A master-regulator sequence motif is now identified that is critical to controlling the aggregation of the αSyn NAC region. Interestingly, this region was also found to be important for membrane vesicle fusion. This master-regulator region could be targeted to prevent αSyn aggregation. The results reveal several unanswered questions about the αSyn aggregation mechanism.