Please use this identifier to cite or link to this item: https://doi.org/10.1002/jnr.21656
Title: Molecular biology changes associated with LRRK2 mutations in Parkinson's disease
Authors: Yi, W.L.
Tan, E.-K. 
Keywords: Kinase activity
Leucine-rich repeat kinase 2
Mutation
Parkinson's disease
Issue Date: Jul-2008
Citation: Yi, W.L., Tan, E.-K. (2008-07). Molecular biology changes associated with LRRK2 mutations in Parkinson's disease. Journal of Neuroscience Research 86 (9) : 1895-1901. ScholarBank@NUS Repository. https://doi.org/10.1002/jnr.21656
Abstract: Parkinson's disease (PD) is characterized by progressive dopaminergic neuronal loss in the substantia nigra. The recent discovery of leucine-rich-repeat kinase 2 gene (LRRK2) mutations in PD is significant because these mutations are the most common cause of autosomal dominant PD. Furthermore, a common recurrent mutation (G2019S) is associated with a significant proportion of nonfamilial PD, and a polymorphic variant (G2385R) has been found to increase the risk in the Asian race. The large LRRK2 protein of 280 kD contains three protein-protein interaction domains and two enzymatic domains, the Ras-related GTPase and the kinase. Mutations in these domains have been described in PD patients. Preliminary evidence suggests that some types of LRRK2 mutations increase the kinase activity, and this is associated with significantly higher apoptotic cell death in dopaminergic cell lines and primary neurons; abolishing the kinase function ameliorates this cellular toxicity. It also appears that its GTPase domain can be activated independently, whereas the kinase activity strictly requires the GTPase activation. Mutations in the LRRK2 have displayed notable pleomorphic pathologies that might indicate an upstream role of LRRK2 in cellular signaling pathways. The identification of physiological substrates (likely to be involved in signaling and apotoptic pathways) of LRRK2 remains an important step in our understanding of the role of LRRK2 in the disease process. Further in vitro and in vivo studies will unravel the role of LRRK2 in cell signaling and its impact on proliferation, differentiation, and survival of neurons. © 2008 Wiley-Liss, Inc.
Source Title: Journal of Neuroscience Research
URI: http://scholarbank.nus.edu.sg/handle/10635/110388
ISSN: 03604012
DOI: 10.1002/jnr.21656
Appears in Collections:Staff Publications

Show full item record
Files in This Item:
There are no files associated with this item.

SCOPUSTM   
Citations

24
checked on Dec 11, 2018

WEB OF SCIENCETM
Citations

23
checked on Dec 3, 2018

Page view(s)

75
checked on Dec 7, 2018

Google ScholarTM

Check

Altmetric


Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.