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Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate
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Metabolic Labeling of Leucine Rich Repeat Kinases 1 and 2 with Radioactive Phosphate

Published on: September 18, 2013

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LRRK2 Phosphorylation, More Than an Epiphenomenon

Antoine Marchand1,2, Matthieu Drouyer1,2, Alessia Sarchione1,2

  • 1University of Lille, Inserm, CHU Lille, U1172 - LilNCog - Lille Neuroscience & Cognition, Lille, France.

Frontiers in Neuroscience
|July 3, 2020
PubMed

Insights

Leucine Rich Repeat Kinase 2 (LRRK2) gene mutations are linked to Parkinson's disease (PD). This review explores how LRRK2 phosphorylation impacts its function and cellular processes relevant to PD pathogenesis.

Area of Science:

  • Neuroscience
  • Genetics
  • Molecular Biology

Background:

  • Mutations in the Leucine Rich Repeat Kinase 2 (LRRK2) gene are a known cause of autosomal dominant Parkinson's disease (PD).
  • Genetic variations in the LRRK2 gene are also associated with an increased risk for developing sporadic PD.
  • LRRK2 is a kinase that undergoes multiphosphorylation, crucial for its physiological and pathological functions.

Purpose of the Study:

  • To review current knowledge on Leucine Rich Repeat Kinase 2 (LRRK2) phosphorylation.
  • To discuss the regulatory mechanisms governing LRRK2 phosphorylation levels.
  • To explore how alterations in LRRK2 phosphorylation affect cellular processes implicated in Parkinson's disease.

Main Methods:

  • Literature review of existing research on LRRK2 phosphorylation.
  • Analysis of evidence linking LRRK2 phosphorylation status to PD pathology.
  • Synthesis of information on LRRK2 phosphoregulation and its cellular consequences.

Main Results:

  • Reduced LRRK2 heterologous phosphorylation is observed in PD brains and upon pharmacological LRRK2 inhibition.
  • Dephosphorylation of LRRK2 at heterologous phosphosites leads to its accumulation in subcellular compartments.
  • The precise regulatory mechanisms and full cellular consequences of LRRK2 phosphorylation changes are not yet fully understood.

Conclusions:

  • LRRK2 phosphorylation plays a critical role in both the normal function and the disease mechanisms of Parkinson's disease.
  • Further research into LRRK2 phosphoregulation is necessary to fully elucidate its connection to PD.
  • Understanding LRRK2 phosphorylation dynamics may reveal novel therapeutic targets for Parkinson's disease.
Keywords:
LRRK2Parkinson's diseasekinasephenotypephosphatasephosphorylation

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