The expression of DJ-1 (PARK7) in normal human CNS and idiopathic Parkinson's disease.
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.
Bandopadhyay
Rina
R
Reta Lila Weston Institute of Neurological Studies, Royal Free and UCL Medical School, 46 Cleveland Street, London W1T 4JF, UK.
Kingsbury
Ann E
AE
Cookson
Mark R
MR
Reid
Andrew R
AR
Evans
Ian M
IM
Hope
Andrew D
AD
Pittman
Alan M
AM
Lashley
Tammaryn
T
Canet-Aviles
Rosa
R
Miller
David W
DW
McLendon
Chris
C
Strand
Catherine
C
Leonard
Andrew J
AJ
Abou-Sleiman
Patrick M
PM
Healy
Daniel G
DG
Ariga
Hiroyashi
H
Wood
Nicholas W
NW
de Silva
Rohan
R
Revesz
Tamas
T
Hardy
John A
JA
Lees
Andrew J
AJ
D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D001253:Astrocytes / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D016631:Lewy Bodies / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism; D015513:Oncogene Proteins / Q000276:immunology / Q000378:metabolism*; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D000071617:Protein Deglycase DJ-1; D020033:Protein Isoforms / Q000378:metabolism; D013378:Substantia Nigra / Q000378:metabolism
D000911:Antibodies, Monoclonal; D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D020033:Protein Isoforms; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1