RGD Reference Report - The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease. - Rat Genome Database

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The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease.

Authors: Bandopadhyay, R  Kingsbury, AE  Cookson, MR  Reid, AR  Evans, IM  Hope, AD  Pittman, AM  Lashley, T  Canet-Aviles, R  Miller, DW  McLendon, C  Strand, C  Leonard, AJ  Abou-Sleiman, PM  Healy, DG  Ariga, H  Wood, NW  De Silva, R  Revesz, T  Hardy, JA  Lees, AJ 
Citation: Bandopadhyay R, etal., Brain. 2004 Feb;127(Pt 2):420-30. Epub 2003 Dec 8.
RGD ID: 10047292
Pubmed: PMID:14662519   (View Abstract at PubMed)
DOI: DOI:10.1093/brain/awh054   (Journal Full-text)

Two mutations in the DJ-1 gene on chromosome1p36 have been identified recently to cause early-onset, autosomal recessive Parkinson's disease. As no information is available regarding the distribution of DJ-1 protein in the human brain, in this study we used a monoclonal antibody for DJ-1 to map its distribution in frontal cortex and substantia nigra, regions invariably involved in Parkinson's disease. Western blotting of human frontal cortex showed DJ-1 to be an abundant protein in control, idiopathic Parkinson's disease, cases with clinical and pathological phenotypes of Parkinson's disease with R98Q polymorphism for DJ-1, and in progressive supranuclear palsy (PSP) brains. We also showed that DJ-1 immunoreactivity (IR) was particularly prominent in astrocytes and astrocytic processes in both control and Parkinson's disease frontal cortex, whereas neurons showed light or no DJ-1 IR. Only occasional Lewy bodies (LBs), the pathological hallmarks of Parkinson's disease, showed faint DJ-1 IR, localized to the outer halo. In preclinical studies we showed that DJ-1 is expressed in primary hippocampal and astrocyte cultures of mouse brain. By 2D gel analysis we also showed multiple pI isoforms for DJ-1 ranging between 5.5-6.6 in both control and Parkinson's disease brains, whilst exposure of M17 cells to the oxidizing agent paraquat was manifested as a shift in pI of endogenous DJ-1 towards more acidic isoforms. We conclude that DJ-1 is not an essential component of LBs and Lewy neurites, is expressed mainly by astrocytes in human brain tissue and is sensitive to oxidative stress conditions. These results are consistent with the hypothesis that neuronal-glial interactions are important in the pathophysiology of Parkinson's disease.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
fertilization involved_inTAS 10047292PMID:14662519ParkinsonsUK-UCL 

Objects Annotated

Genes (Rattus norvegicus)
Park7  (Parkinsonism associated deglycase)


Additional Information