APS -2017 Annual Meeting of the APS Mid-Atlantic Section- Event - $alpha -$synuclein aggregation and inhibition: the role of $eta $-synuclein

摘要

$alpha -$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 $eta $-synuclein ($eta $S) co-localizes with $alpha $S and can act as a neuro-protector of $alpha $S toxicity extit{in vivo }to inhibit pathological $alpha $S aggregation. Using NMR and biophysical approaches, we will discuss the molecular mechanisms of $alpha $S inhibition by $eta $S and demonstrate the presence of an environmentally sensitive pH switch for $eta $S that serves as an on/off fibrillation switch at mildly acidic physiological pH. These results have several implications for the role of $eta $S in disease and highlight the complex interplay of $alpha $S and $eta $S in the cell.