Experimental modelling of -synuclein aggregation and spreading in synucleinopathies

Abstract

During the past two decades, a myriad of studies have suggested a central pathogenic role for a-synuclein in Parkinson's disease. Recent studies have unravelled self-aggregation and prion-like spreading properties for a-synuclein. Of particular importance was the seminal observation of Lewy body-like structures in grafted fetal dopaminergic neurons of patients with Parkinson's disease. This conceptual breakthrough generated the " host-to-the-graft " hypothesis orprion-like hypothesis. Nowadays, mechanisms underlying these new properties appear as putative disease-modifying targets. As the lack of valid animal models for Parkinson's disease is considered as a roadblock toward therapeutic intervention, the use of the newly developed models based on the prion-like properties of a-synuclein should allow future target validation.