How Are Synaptic Vesicle Exocytosis and Endocytosis Affected in Parkinson Disease?

Synaptic vesicle exocytosis and endocytosis are 2 fundamental processes that involve the coordinated and timely activity of many proteins and protein-lipid interactions. Alpha-synuclein (α-Syn) regulates several steps of these processes. Impaired exocytosis and endocytosis are important consequences of Parkinson disease (PD), reflecting both loss of function of normal α-Syn and toxic gain of function of abnormal α-Syn aggregates. Studies in familial forms of PD indicate that abnormal functions of other critical proteins such as leucine repeat rich kinase 2 also impair normal synaptic vesicular trafficking and contribute to synaptic dysfunction and secondary neurodegeneration.