Abstract
Macroautophagy (hereafter autophagy) and endocytic trafficking are key pathways in neuronal axons that regulate the composition and integrity of the axonal proteome. These pathways have similar trafficking itineraries; however, the extent of their cross-talk remains incompletely understood. Our recent work demonstrates that under physiological conditions, axonal autophagy and endocytic pathways are separate and exhibit distinct rates of organelle maturation. Strikingly, overexpression of pathogenic α-synuclein disrupts the segregation between these pathways by merging autophagosomes and endosomes generated in the distal axon. These results raise the possibility that precocious degradation of endocytosed cargo via misrouting into lysosome-destined autophagosomes may contribute to neuronal dysfunction in Parkinson disease and related α-synucleinopathies.