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Updated: Aug 4, 2026

Assaying the Kinase Activity of LRRK2 in vitro
06:09

Assaying the Kinase Activity of LRRK2 in vitro

Published on: January 18, 2012

LRRK2-mediated Rab10 phosphorylation in immune cells from Parkinson's disease patients

Farzaneh Atashrazm1, Deborah Hammond2, Gayathri Perera1

  • 1Brain and Mind Centre, Central Clinical School, University of Sydney, Camperdown, NSW, Australia.

Movement Disorders : Official Journal of the Movement Disorder Society
|January 1, 2019
PubMed
Abstract

Insights

Rab10 T73 phosphorylation is a valid biomarker for Leucine-rich repeat kinase 2 inhibitor trials in Parkinson's disease. However, its use as a patient enrichment biomarker is complicated, though increased Leucine-rich repeat kinase 2 in neutrophils may aid stratification.

Area of Science:

  • Neuroscience
  • Biochemistry
  • Pharmacology

Background:

  • Leucine-rich repeat kinase 2 (LRRK2) is a key therapeutic target for Parkinson's disease (PD).
  • LRRK2 inhibitors are under clinical development for PD treatment.
  • Identifying reliable biomarkers is crucial for LRRK2 inhibitor clinical trials.

Purpose of the Study:

  • To assess Rab10 phosphorylation as a biomarker for LRRK2 inhibitor trials.
  • To evaluate Rab10 as a target engagement biomarker (TEB).
  • To explore Rab10's potential as a patient enrichment biomarker (PEB) for LRRK2 inhibitor studies.

Main Methods:

  • Peripheral blood mononuclear cells (PBMCs) and neutrophils were isolated from PD patients and controls.
  • Cells were treated ex vivo with an LRRK2 inhibitor.
  • Immunoblotting measured LRRK2 and Rab10 levels and phosphorylation; plasma cytokines were measured via ELISA.

Main Results:

  • PBMCs and neutrophils from PD patients and controls responded similarly to LRRK2 inhibition.
  • LRRK2 levels were similar in PD patient and control PBMCs but elevated in PD neutrophils.
  • Rab10 T73 phosphorylation levels were similar in both groups and did not correlate with LRRK2 levels.

Conclusions:

  • Rab10 T73 phosphorylation is a promising TEB for LRRK2 inhibitor trials.
  • The lack of correlation between LRRK2 and Rab10 phosphorylation limits Rab10's utility as a PEB.
  • Elevated LRRK2 in PD neutrophils may offer potential for patient stratification.
  • LRRK2 activity in immune cells might contribute to PD's inflammatory phenotype.
Keywords:
Parkinson's diseaseRab GTPasebiomarkerbloodinflammation

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