The Parkinson's disease gene DJ-1 is also a key regulator of stroke-induced damage.
Recent evidence has indicated that common mechanisms play roles among multiple neurological diseases. However, the specifics of these pathways are not completely understood. Stroke is caused by the interruption of blood flow to the brain, and cumulative evidence supports the critical role of oxidative stress in the ensuing neuronal death process. DJ-1 (PARK7) has been identified as the gene linked to early-onset familial Parkinson's disease. Currently, our work also shows that DJ-1 is central to death in both in Vitro and in Vivo models of stroke. Loss of DJ-1 increases the sensitivity to excitotoxicity and ischemia, whereas expression of DJ-1 can reverse this sensitivity and indeed provide further protection. Importantly, DJ-1 expression decreases markers of oxidative stress after stroke insult in Vivo, suggesting that DJ-1 protects through alleviation of oxidative stress. Consistent with this finding, we demonstrate the essential role of the oxidation-sensitive cysteine-106 residue in the neuroprotective activity of DJ-1 after stroke. Our work provides an important example of how a gene seemingly specific for one disease, in this case Parkinson's disease, also appears to be central in other neuropathological conditions such as stroke. It also highlights the important commonalities among differing neuropathologies.
Aleyasin
Hossein
H
Ottawa Health Research Institute, Neuroscience Group, University of Ottawa, 451 Smyth Road, Ottawa, ON, Canada K1H 8M5.
Rousseaux
Maxime W C
MW
Phillips
Maryam
M
Kim
Raymond H
RH
Bland
Ross J
RJ
Callaghan
Steve
S
Slack
Ruth S
RS
During
Matthew J
MJ
Mak
Tak W
TW
Park
David S
DS
D000818:Animals; D015415:Biomarkers; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003545:Cysteine / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008869:Microtubule-Associated Proteins / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D015513:Oncogene Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D054464:Peroxiredoxins; D000071617:Protein Deglycase DJ-1; D051381:Rats; D012680:Sensitivity and Specificity; D020521:Stroke / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*
D015415:Biomarkers; D008869:Microtubule-Associated Proteins; D015513:Oncogene Proteins; D054464:Peroxiredoxins; C503466:PARK7 protein, mouse; C404267:PARK7 protein, rat; D000071617:Protein Deglycase DJ-1; D003545:Cysteine