Linked Life Data

19878656

Source:http://linkedlifedata.com/resource/pubmed/id/19878656

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-11-30
pubmed:abstractText
Mutations of the leucine-rich repeat kinase 2 (LRRK2) gene are the leading cause of genetically inherited Parkinson's disease (PD) and its more severe variant diffuse Lewy body disease (DLB). Pathological mutations in Lrrk2 are autosomal dominant, suggesting a gain of function. Mutations in alpha-synuclein also produce autosomal dominant disease. Here we report an interaction between Lrrk2 and alpha-synuclein in a series of diffuse Lewy body (DLB) cases and in an oxidative stress cell based assay. All five cases of DLB, but none of five controls, showed co-immunoprecipitation of Lrrk2 and alpha-synuclein in soluble brain extracts. Colocalization was also found in pathological deposits in DLB postmortem brains by double immunostaining. In HEK cells transfected simultaneously with plasmids expressing Lrrk2 and alpha-synuclein, co-immunoprecipitation of Lrrk2 and alpha-synuclein was detected when they were exposed to oxidative stress by H(2)O(2). Taken together, these results suggest the possibility that in PD and related synucleinopathies, oxidative stress upregulates alpha-syn and Lrrk2 expression, paving the way for pathological interactions. New therapeutic approaches to PD and the synucleinopathies may result from limiting the interaction between Lrrk2 and alpha-synuclein.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
25
pubmed:volume
390
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1229-34
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Lrrk2 interaction with alpha-synuclein in diffuse Lewy body disease.
pubmed:affiliation
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, British Columbia, Canada V6T 1Z3.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't