$\alpha -$synuclein aggregation and inhibition: the role of $\beta $-synuclein

$\alpha -$synuclein ($\alpha $S) is a small neuronal intrinsically disordered protein (IDP) that self-associates to form oligomers and fibrils in the brains of patients with Parkinson's disease. The highly homologous protein $\beta $-synuclein ($\beta $S) co-localizes with $\alpha $S and can act as a neuro-protector of $\alpha $S toxicity \textit{in vivo }to inhibit pathological $\alpha $S aggregation. Using NMR and biophysical approaches, we will discuss the molecular mechanisms of $\alpha $S inhibition by $\beta $S and demonstrate the presence of an environmentally sensitive pH switch for $\beta $S that serves as an on/off fibrillation switch at mildly acidic physiological pH. These results have several implications for the role of $\beta $S in disease and highlight the complex interplay of $\alpha $S and $\beta $S in the cell.