Document Detail


LRRK2 expression in normal and pathologic human brain and in human cell lines.
MedLine Citation:
PMID:  17021400     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Mutations in the leucine-rich repeat kinase 2 gene (LRRK2) have been recently identified in families with autosomal-dominant late-onset Parkinson disease. We report that by reverse transcriptase-polymerase chain reaction, the mRNA of LRRK2 is expressed in soluble extracts of human brain, liver, and heart and in cultured human astrocytes, microglia, and oligodendroglia as well as in human neuroblastoma cell lines. We find by Western blotting using a polyclonal antibody of the leucine-rich repeat kinase 2 protein (Lrrk2) specific for C-terminal residues 2,511-2,527 that an apparent full-length protein and several of its fractions are expressed in soluble extracts of normal human brain. By immunocytochemistry, the antibody recognizes neurons, and more weakly astrocytes and microglia, in normal brain tissue. It intensely labels Lewy bodies in Parkinson disease and related neurodegenerative disorders. It also labels a subset of neurofibrillary tangles in Alzheimer disease and the Parkinsonism dementia complex of Guam (PDCG). It labels thorn-shaped astrocytes and oligodendroglial coiled bodies in PDCG; oligodendroglial inclusions in multiple system atrophy; Pick bodies in Pick disease; nuclear and cytoplasmic inclusions in Huntington disease; and intraneuronal and glial inclusions in amyotrophic lateral sclerosis. In summary, LRRK2 is constitutively expressed in neurons and also in glial cells of human brain. It strongly associates with pathological inclusions in several neurodegenerative disorders.
Authors:
Judith Miklossy; Tetsuaki Arai; Jian-Ping Guo; Andis Klegeris; Sheng Yu; Edith G McGeer; Patrick L McGeer
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of neuropathology and experimental neurology     Volume:  65     ISSN:  0022-3069     ISO Abbreviation:  J. Neuropathol. Exp. Neurol.     Publication Date:  2006 Oct 
Date Detail:
Created Date:  2006-10-05     Completed Date:  2006-11-14     Revised Date:  2012-06-25    
Medline Journal Info:
Nlm Unique ID:  2985192R     Medline TA:  J Neuropathol Exp Neurol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  953-63     Citation Subset:  IM    
Affiliation:
Kinsmen Laboratory of Neurological Research, University of British Columbia, Vancouver, BC, Canada.
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MeSH Terms
Descriptor/Qualifier:
Adult
Aged
Aged, 80 and over
Astrocytes / metabolism
Biological Markers / analysis*
Blotting, Western
Brain / metabolism*,  pathology
Cells, Cultured
Female
Humans
Immunohistochemistry
Liver / metabolism
Male
Microglia / metabolism
Middle Aged
Myocardium / metabolism
Neurodegenerative Diseases / metabolism*,  pathology
Oligodendroglia / metabolism
Protein-Serine-Threonine Kinases / biosynthesis*
RNA, Messenger / analysis
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Biological Markers; 0/RNA, Messenger; EC 2.7.11.1/LRRK2 protein, human; EC 2.7.11.1/Protein-Serine-Threonine Kinases

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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