The role of autophagy in synucleinopathy: clearance versus spread of α-synuclein.

Emerging evidence suggests that the propagation of α-synuclein pathology underlies the progression of Parkinson's disease and supports the hypothesis that transmission of α-synuclein aggregates contributes to dopaminergic degeneration. Autophagy, a cellular degradation process, removes protein aggregates and damaged organelles and aids in α-synuclein clearance. However, fibrillar α-synuclein aggregates may evade and even disrupt autophagy, causing toxic spread. The role of autophagy may be multifaceted in the propagation of α-synuclein: clearing α-synuclein aggregates and damaged organelles (protective) versus the release of α-synuclein aggregates (harmful). Here we review how neuronal and glial autophagy regulate α-synuclein clearance and spreading. We also discuss the need for future research to address the interplay of autophagy and α-synuclein aggregates toward therapeutic development.