TY - JOUR
TI - Elevated In Vitro Kinase Activity in Peripheral Blood Mononuclear Cells
ofLeucine-RichRepeat Kinase 2G2019SCarriers: A
NovelEnzyme-LinkedImmunosorbent Assay-Based Method
AU - Melachroinou, Katerina
AU - Kang, Min Suk
AU - Liong, Christopher and
AU - Narayan, Sushma
AU - Levers, Najah
AU - Joshi, Neal
AU - Kopil, Katie and
AU - Hutten, Samantha J.
AU - Baptista, Marco A. S.
AU - Padmanabhan, Shalini
AU - and Kang, Un Jung
AU - Stefanis, Leonidas
AU - Alcalay, Roy N. and
AU - Rideout, Hardy J.
JO - Movement disorders : official journal of the Movement Disorder Society
PY - 2020
VL - 35
TODO - 11
SP - 2095-2100
PB - Wiley
SN - null
TODO - 10.1002/mds.28175
TODO - ELISA; kinase; LRRK2; Parkinson's disease; PBMC
TODO - 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. (c) 2020 International Parkinson and
Movement Disorder Society
ER -