The LRRK2-macroautophagy axis and its relevance to Parkinson's disease

Biochem Soc Trans. 2017 Feb 8;45(1):155-162. doi: 10.1042/BST20160265.

Abstract

A wide variety of different functions and an impressive array of interactors have been associated with leucine-rich repeat kinase 2 (LRRK2) over the years. Here, I discuss the hypothesis that LRRK2 may be capable of interacting with different proteins at different times and places, therefore, controlling a plethora of diverse functions based on the different complexes formed. Among these, I will then focus on macroautophagy in the general context of the endolysosomal system. First, the relevance of autophagy in Parkinson's disease will be evaluated giving a brief overview of all the relevant Parkinson's disease genes; then, the association of LRRK2 with macroautophagy and the endolysosomal pathway will be analyzed based on the supporting literature.

Keywords: Parkinson's disease; autophagy; leucine-rich repeat kinase; neurodegeneration.

Publication types

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

MeSH terms

  • Autophagy*
  • Endosomes / metabolism
  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / metabolism*
  • Lysosomes / metabolism
  • Models, Biological
  • Mutation
  • Parkinson Disease / enzymology*
  • Parkinson Disease / genetics
  • Parkinson Disease / metabolism
  • Protein Binding
  • Signal Transduction*
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism
  • alpha-Synuclein / genetics
  • alpha-Synuclein / metabolism

Substances

  • SNCA protein, human
  • VPS35 protein, human
  • Vesicular Transport Proteins
  • alpha-Synuclein
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2