Autophagy at the synapse, an early site of dysfunction in neurodegeneration

Macroautophagy, herein referred to as autophagy, has long been implicated in the pathophysiology of neurodegenerative diseases. However, an incomplete understanding of how autophagy contributes to disease pathogenesis has limited progress in acting on this potential target for the development of disease-modifying therapeutics. Research in the past few decades has revealed that autophagy plays a specialized role in the synapse, a site of early dysfunction in multiple neurodegenerative diseases. In this review, we discuss the evidence suggesting that inadequate autophagy at the synapse may contribute to neurodegeneration, and why the functions of autophagy may be particularly relevant for synaptic function.