A Parkinson's disease gene, DJ-1, repairs brain injury through Sox9 stabilization and astrogliosis.
Dong-Joo ChoiJin-Hwa EunByung Gon KimIlo JouSang Myun ParkEun-Hye JoePublished in: Glia (2017)
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.
Keyphrases
- brain injury
- cerebral ischemia
- subarachnoid hemorrhage
- wild type
- resting state
- white matter
- transcription factor
- magnetic resonance imaging
- stem cells
- functional connectivity
- genome wide
- poor prognosis
- blood brain barrier
- copy number
- single cell
- spinal cord
- metabolic syndrome
- binding protein
- cell therapy
- high fat diet induced
- dna methylation
- respiratory failure
- ultrasound guided
- hepatitis b virus
- skeletal muscle
- gene expression
- contrast enhanced
- small molecule
- insulin resistance
- intensive care unit
- mesenchymal stem cells
- drug induced
- amino acid