Dysfunction of the autophagy/lysosomal degradation pathway is a shared feature of the genetic synucleinopathies

FASEB J. 2013 Sep;27(9):3424-9. doi: 10.1096/fj.12-223842. Epub 2013 May 16.

Abstract

The past decade has witnessed huge advances in our understanding of the genetics underlying Parkinson's disease. Identifying commonalities in the biological function of genes linked to Parkinson's provides an opportunity to elucidate pathways that lead to neuronal degeneration and eventually to disease. We propose that the genetic forms of Parkinson's disease largely associated with α-synuclein-positive neuropathology (SNCA, LRRK2, and GBA) are brought together by involvement in the autophagy/lysosomal pathway and that this represents a unifying pathway to disease in these cases.

Keywords: GBA; LRRK2; Parkinson's disease.

Publication types

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

MeSH terms

  • Animals
  • Autophagy / genetics
  • Autophagy / physiology*
  • Humans
  • Lysosomes / metabolism*
  • Models, Biological
  • Nerve Degeneration / genetics
  • Nerve Degeneration / metabolism*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism*
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism*

Substances

  • alpha-Synuclein