Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2008-6-23
pubmed:abstractText
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 apoptotic 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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1097-4547
pubmed:author
pubmed:copyrightInfo
2008 Wiley-Liss, Inc.
pubmed:issnType
Electronic
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1895-901
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Molecular biology changes associated with LRRK2 mutations in Parkinson's disease.
pubmed:affiliation
Department of Neurology, Singapore General Hospital, Singapore.
pubmed:publicationType
Journal Article, Review