Autophagy and proteostasis in the control of synapse aging and disease.

The maintenance of neuronal homeostasis is severely threatened by aging, probably partially due to compromised autophagic clearance. Hence, rejuvenating autophagy in aging neurons is considered a promising strategy to restore cognitive performance. Research in recent years has shown that autophagosome biogenesis takes place mainly in distal axons and, thus, close to presynaptic specializations, and that efficient macro-autophagy is essential for neuronal homeostasis and survival. Retrograde transport of autophagosomes might play a role in neuronal signaling processes, promoting neuronal complexity and preventing neurodegeneration. Here, we discuss recent advances concerning the intersection of aging, neurodegeneration and autophagy, and try to create a unified view of how neuronal autophagy and proteostasis might control synaptic aging and disease.