A Parkinson's disease gene, DJ-1, repairs brain injury through Sox9 stabilization and astrogliosis.
Glia
; 66(2): 445-458, 2018 02.
Article
em En
| MEDLINE
| ID: mdl-29105838
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.
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Base de dados:
MEDLINE
Assunto principal:
Lesões Encefálicas
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Astrócitos
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Fatores de Transcrição SOX9
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Proteína Desglicase DJ-1
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Gliose
Limite:
Animals
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article