Τίτλος:
Elevated In Vitro Kinase Activity in Peripheral Blood Mononuclear Cells
ofLeucine-RichRepeat Kinase 2G2019SCarriers: A
NovelEnzyme-LinkedImmunosorbent Assay-Based Method
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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
Συγγραφείς:
Melachroinou, Katerina
Kang, Min Suk
Liong, Christopher and
Narayan, Sushma
Levers, Najah
Joshi, Neal
Kopil, Katie and
Hutten, Samantha J.
Baptista, Marco A. S.
Padmanabhan, Shalini
and Kang, Un Jung
Stefanis, Leonidas
Alcalay, Roy N. and
Rideout, Hardy J.
Περιοδικό:
Movement disorders : official journal of the Movement Disorder Society
Λέξεις-κλειδιά:
ELISA; kinase; LRRK2; Parkinson's disease; PBMC
