Presynaptic endocytic factors in autophagy and neurodegeneration

Curr Opin Neurobiol. 2018 Feb;48:153-159. doi: 10.1016/j.conb.2017.12.018. Epub 2018 Jan 6.

Abstract

Neuronal signaling depends on the exocytic fusion and subsequent endocytic retrieval and reformation of neurotransmitter-containing synaptic vesicles at synapses. Recent findings have uncovered surprising roles of presynaptic endocytic proteins in the formation and transport of autophagosomes. These include functions of the membrane remodelling protein endophilin and its downstream effector, the phosphoinositide phosphatase synaptojanin, in autophagosome formation and in Parkinson's disease, the endocytic sorting adaptor CALM in protein degradation via the autophagy/lysosomal pathway in Alzheimer's disease, and the clathrin adaptor complex AP-2 in retrograde transport of signaling autophagosomes to prevent neurodegeneration. These findings reveal unanticipated connections between the machineries for synaptic neurotransmission and neuronal proteostasis and identify presynaptic endocytic proteins as potential targets to treat neurodegenerative diseases.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acyltransferases / metabolism
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Autophagy / physiology*
  • Endocytosis / physiology*
  • Humans
  • Nerve Degeneration / metabolism
  • Nerve Degeneration / pathology*
  • Presynaptic Terminals / physiology*

Substances

  • Adaptor Proteins, Vesicular Transport
  • Acyltransferases
  • 2-acylglycerophosphate acyltransferase