Living in Α-Syn: Tackling Aggregates in Parkinson's Disease.

How do protein aggregates contribute to neurodegenerative disorders, and can they be therapeutically targeted? In this issue of Neuron, Stojkovska et al. (2022) show that aggregated α-synuclein disrupts ER and lysosomal function in Parkinson's disease patient-derived neurons and that combined enhancement of multiple arms of the proteostasis network improves these defects.