scholarly journals Differential Inhibition of LRRK2 in Parkinson's Disease Patient Blood by a G2019S Selective LRRK2 Inhibitor

2021 ◽  
Author(s):  
Jessica M. Bright ◽  
Holly J. Carlisle ◽  
Alyssa M. A. Toda ◽  
Molly Murphy ◽  
Tyler P. Molitor ◽  
...  

2021 ◽  
pp. 1-9
Author(s):  
Laura P. Hughes ◽  
Marilia M.M. Pereira ◽  
Deborah A. Hammond ◽  
John B. Kwok ◽  
Glenda M. Halliday ◽  
...  

Background: Reduced activity of lysosomal glucocerebrosidase is found in brain tissue from Parkinson’s disease patients. Glucocerebrosidase is also highly expressed in peripheral blood monocytes where its activity is decreased in Parkinson’s disease patients, even in the absence of GBA mutation. Objective: To measure glucocerebrosidase activity in cryopreserved peripheral blood monocytes from 30 Parkinson’s disease patients and 30 matched controls and identify any clinical correlation with disease severity. Methods: Flow cytometry was used to measure lysosomal glucocerebrosidase activity in total, classical, intermediate, and non-classical monocytes. All participants underwent neurological examination and motor severity was assessed by the Movement Disorders Society Unified Parkinson’s Disease Rating Scale. Results: Glucocerebrosidase activity was significantly reduced in the total and classical monocyte populations from the Parkinson’s disease patients compared to controls. GCase activity in classical monocytes was inversely correlated to motor symptom severity. Conclusion: Significant differences in monocyte glucocerebrosidase activity can be detected in Parkinson’s disease patients using cryopreserved mononuclear cells and monocyte GCase activity correlated with motor features of disease. Being able to use cryopreserved cells will facilitate the larger multi-site trials needed to validate monocyte GCase activity as a Parkinson’s disease biomarker.





2012 ◽  
Vol 24 (3) ◽  
pp. 104-113 ◽  
Author(s):  
Jae-Song Choi ◽  
Moon-Hee Jang ◽  
Taek-Won Ahn


2011 ◽  
Vol 27 (2) ◽  
pp. 325-326 ◽  
Author(s):  
Takashi Asahi ◽  
Yukichi Inoue ◽  
Nakamasa Hayashi ◽  
Kazutomi Araki ◽  
Shunro Endo


2020 ◽  
Vol 45 ◽  
pp. 101828
Author(s):  
Hidefumi Suzuki ◽  
Naohiro Egawa ◽  
Takayuki Kondo ◽  
Keiko Imamura ◽  
Takako Enami ◽  
...  


2019 ◽  
Vol Volume 9 ◽  
pp. 29-42 ◽  
Author(s):  
Patricia Gillivan-Murphy ◽  
Nick Miller ◽  
Paul Carding


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