Selective inhibition of LRRK2 activity as an approach to the treatment of Parkinson's disease
https://doi.org/10.25557/2073-7998.2022.12.26-29
Abstract
To date, there are no neuroprotective drugs for the common neurodegenerative disease, Parkinson’s disease (PD). PD associated with mutations in the GBA gene (GBA-PD) is the most common form of PD with a known etiology. GBA-PD is considered the most promising for the development of therapy for PD. Mutations in the GBA gene encoding the enzyme glucocerebrosidase (GCase) lead to a decrease in the activity of this enzyme. Previously, it was shown that inhibition of LRRK2 kinase activity by MLi-2 inhibitor leads to an increase in GCase activity. In this study, we showed for the first time the effect of the LRRK2 kinase activity inhibitor MLi-2 not only on the activity of GCase, but also on the activity of other lysosomal enzymes in the primary culture of peripheral blood macrophages of patients with LRRK2-associated PD (LRRK2-PD) and GBA-PD.
About the Authors
T. S. Usenko
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»; Pavlov First Saint-Petersburg State Medical University
Russian Federation
Russian Federation
K. S. Basharova
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»
Russian Federation
Russian Federation
A. I. Bezrukova
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»
Russian Federation
Russian Federation
M. A. Nikolaev
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»; Pavlov First Saint-Petersburg State Medical University
Russian Federation
Russian Federation
I. V. Miliukhina
Pavlov First Saint-Petersburg State Medical University; Institute of the Human Brain RAS
Russian Federation
Russian Federation
G. V. Baydakova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
E. Y. Zakharova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
S. N. Pchelina
Petersburg Nuclear Physics Institute named by B.P. Konstantinov of National Research Centre «Kurchatov Institute»; Pavlov First Saint-Petersburg State Medical University
Russian Federation
Russian Federation
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Review
For citations:
Usenko T.S., Basharova K.S., Bezrukova A.I., Nikolaev M.A., Miliukhina I.V., Baydakova G.V., Zakharova E.Y., Pchelina S.N. Selective inhibition of LRRK2 activity as an approach to the treatment of Parkinson's disease. Medical Genetics. 2022;21(12):26-29. (In Russ.) https://doi.org/10.25557/2073-7998.2022.12.26-29
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