Differential DJ-1 gene expression in Parkinson's disease.
Mutations in the DJ-1 gene have been linked with rare cases of early onset, autosomal recessive Parkinson's disease (PD). To determine whether DJ-1 is also involved in the pathogenesis of common forms of PD we have compared DJ-1 mRNA levels in a number of post-mortem PD and control brain regions using quantitative real-time PCR. Region-specific decreases were observed in DJ-1 mRNA levels in putamen, frontal cortex, parietal cortex and cerebellum in PD ( approximately 30-60%) compared to controls whilst an up-regulation was observed in the amygdala ( approximately 90%) and entorhinal cortex ( approximately 39%). Using quantitative western blot analysis, parallel decreases in DJ-1 protein levels were seen in frontal cortex, putamen and cerebellum of PD cases. By using 2-dimensional gel electrophoresis, we show preponderance of acidic pI isoforms of DJ-1 monomer in PD vulnerable regions, namely frontal cortex and medulla suggestive of differential post-translational modifications. Our findings point to a putative role of DJ-1 in the pathogenesis of PD.
Kumaran
Ravindran
R
Reta Lila Weston Institute of Neurological Disease, Institute of Neurology, University College London, 1, Wakefield Street, WC1N 1PJ, UK.
Vandrovcova
Jana
J
Luk
Connie
C
Sharma
Simone
S
Renton
Alan
A
Wood
Nicholas W
NW
Hardy
John A
JA
Lees
Andrew J
AJ
Bandopadhyay
Rina
R
D000368:Aged; D000369:Aged, 80 and over; D000679:Amygdala / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D018728:Entorhinal Cortex / Q000378:metabolism; D005260:Female; D005625:Frontal Lobe / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015513:Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics*; D010296:Parietal Lobe / Q000378:metabolism; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D000071617:Protein Deglycase DJ-1; D011699:Putamen / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D015854:Up-Regulation / Q000235:genetics
D047908:Intracellular Signaling Peptides and Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; C105131:PARK7 protein, human; D000071617:Protein Deglycase DJ-1