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A Parkinson's disease gene, DJ-1, repairs brain injury through Sox9 stabilization and astrogliosis

Authors
Choi, DJ  | Eun, JH | Kim, BG  | Jou, I  | Park, SM  | Joe, EH
Citation
Glia, 66(2). : 445-458, 2018
Journal Title
Glia
ISSN
0894-14911098-1136
Abstract
Defects in repair of damaged brain accumulate injury and contribute to slow-developing neurodegeneration. Here, we report that a deficiency of DJ-1, a Parkinson's disease (PD) gene, delays repair of brain injury due to destabilization of Sox9, a positive regulator of astrogliosis. Stereotaxic injection of ATP into the brain striatum produces similar size of acute injury in wild-type and DJ-1-knockout (KO) mice. However, recovery of the injury is delayed in KO mice, which is confirmed by 9.4T magnetic resonance imaging and tyrosine hydroxylase immunostaining. DJ-1 regulates neurite outgrowth from damaged neurons in a non-cell autonomous manner. In DJ-1 KO brains and astrocytes, Sox9 protein levels are decreased due to enhanced ubiquitination, resulting in defects in astrogliosis and glial cell-derived neurotrophic factor/ brain-derived neurotrophic factor expression in injured brain and astrocytes. These results indicate that DJ-1 deficiency causes defects in astrocyte-mediated repair of brain damage, which may contribute to the development of PD.
Keywords
MeSH

DOI
10.1002/glia.23258
PMID
29105838
Appears in Collections:
Journal Papers > Research Organization > Inflamm-aging Translational Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Brain Science
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
Ajou Authors
김, 병곤  |  박, 상면  |  조, 은혜  |  주, 일로  |  최, 동주
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