@misc{10481/76497,
year = {2022},
month = {6},
url = {http://hdl.handle.net/10481/76497},
abstract = {Mutations in LRRK2 and GBA1 are key contributors to genetic risk of developing Parkinson’s
disease (PD). To investigate how LRRK2 kinase activity interacts with GBA and contributes to
lysosomal dysfunctions associated with the pathology of PD. The activity of the lysosomal enzyme
 -Glucocerebrosidase (GCase) was assessed in a human neuroglioma cell model treated with two selective
inhibitors of LRKK2 kinase activity (LRRK2-in-1 and MLi-2) and a GCase irreversible inhibitor,
condutirol-beta-epoxide (CBE), under 24 and 72 h experimental conditions. We observed levels of
GCase activity comparable to controls in response to 24 and 72 h treatments with LRRK2-in-1 and
MLi-2. However, GBA protein levels increased upon 72 h treatment with LRRK2-in-1. Moreover,
LC3-II protein levels were increased after both 24 and 72 h treatments with LRRK2-in-1, suggesting
an activation of the autophagic pathway. These results highlight a possible regulation of lysosomal
function through the LRRK2 kinase domain and suggest an interplay between LRRK2 kinase activity
and GBA. Although further investigations are needed, the enhancement of GCase activity might
restore the defective protein metabolism seen in PD.},
organization = {Foundation "Progreso y Salud" of the Junta de Andalucia	PI-0424-2014},
organization = {Programa Operativo FEDER de Andalucia	B-CTS-702-UGR20},
organization = {German Research Foundation (DFG)	EST16/00809	
FPU14/03473},
organization = {UK Research & Innovation (UKRI)},
organization = {Medical Research Council UK (MRC)},
organization = {European Commission	MR/N026004/1	
MR/L010933/1},
publisher = {MDPI},
keywords = {LRRK2},
keywords = {Lysosomal dysfunction},
keywords = {Glucocerebrosidase},
keywords = {Parkinson's disease},
keywords = {Autophagy},
title = {Seventy-Two-Hour LRRK2 Kinase Activity Inhibition Increases Lysosomal GBA Expression inH4, a Human Neuroglioma Cell Line},
doi = {10.3390/ijms23136935},
author = {Ruz, Clara and Alcantud, José Luis and Vives Montero, Francisco and Arrebola Vargas, Francisco Jesús and Durán Ogalla, Raquel},
}