LRRK2 signaling in neurodegeneration: two decades of progress

Essays Biochem. 2021 Dec 22;65(7):859-872. doi: 10.1042/EBC20210013.

Abstract

Leucine-rich repeat kinase 2 (LRRK2) is a complex GTPase/kinase orchestrating cytoskeletal dynamics and multiple steps of the endolysosomal pathway through interaction with a host of partners and phosphorylation of a subset of Rab GTPases. Mutations in LRRK2 cause late-onset Parkinson's disease (PD) and common variants in the locus containing LRRK2 have been associated with sporadic PD, progressive supranuclear palsy as well as a number of inflammatory diseases. This review encompasses the major discoveries in the field of LRRK2 pathobiology, from the initial gene cloning to the latest progress in LRRK2 inhibition as a promising therapeutic approach to fight neurodegeneration.

Keywords: LRRK2; cytoskeleton; glia; inflammation; kinase inhibition; vesicular pathways.

Publication types

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

MeSH terms

  • Humans
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / genetics
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2 / metabolism
  • Lysosomes / metabolism
  • Mutation
  • Parkinson Disease* / genetics
  • Parkinson Disease* / metabolism
  • Phosphorylation
  • Signal Transduction

Substances

  • LRRK2 protein, human
  • Leucine-Rich Repeat Serine-Threonine Protein Kinase-2