Elevated In Vitro Kinase Activity in Peripheral Blood Mononuclear Cells of Leucine-Rich Repeat Kinase 2 G2019S Carriers: A Novel Enzyme-Linked Immunosorbent Assay–Based Method

Katerina Melachroinou, Min Suk Kang, Christopher Liong, Sushma Narayan, Najah Levers, Neal Joshi, Katie Kopil, Samantha J. Hutten, Marco A.S. Baptista, Shalini Padmanabhan, Un Jung Kang, Leonidas Stefanis, Roy N. Alcalay, Hardy J. Rideout*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Leucine-rich repeat kinase 2 kinase inhibitors are being vigorously pursued as potential therapeutic options; however, there is a critical need for sensitive and quantitative assays of leucine-rich repeat kinase 2 function and target engagement. Objectives: Our objective was to compare collection and storage protocols for peripheral blood mononuclear cells, and to determine the optimal conditions for downstream analyses of leucine-rich repeat kinase 2 in PD cohorts. Methods: Here, we describe enzyme-linked immunosorbent assay–based assays capable of detecting multiple aspects of leucine-rich repeat kinase 2 function at endogenous levels in human tissues. Results: In peripheral blood mononuclear cells from both healthy and affected carriers of the G2019S mutation in leucine-rich repeat kinase 2, we report, for the first time, significantly elevated in vitro kinase activity, while detecting a significant increase in pS935/leucine-rich repeat kinase 2 in idiopathic PD patients. Conclusions: Quantitative assays such as these described here could potentially uncover specific markers of leucine-rich repeat kinase 2 function that are predictive of disease progression, aid in patient stratification, and be a critical component of upcoming clinical trials.

Original languageEnglish
Pages (from-to)2095-2100
Number of pages6
JournalMovement Disorders
Volume35
Issue number11
DOIs
StatePublished - Nov 2020
Externally publishedYes

Funding

FundersFunder number
Parkinson’s Foundation
Parkinson’s and Movement Disorder Foundation
National Institutes of Health
Michael J. Fox Foundation for Parkinson's Research
Jain Foundation
Roche
Sanofi
American Parkinson Disease Association
European CommissionH2020

    Keywords

    • ELISA
    • kinase
    • LRRK2
    • Parkinson's disease
    • PBMC

    Fingerprint

    Dive into the research topics of 'Elevated In Vitro Kinase Activity in Peripheral Blood Mononuclear Cells of Leucine-Rich Repeat Kinase 2 G2019S Carriers: A Novel Enzyme-Linked Immunosorbent Assay–Based Method'. Together they form a unique fingerprint.

    Cite this