Cell-specific overexpression of COMT in dopaminergic neurons of Parkinson's disease.
Brain
; 142(6): 1675-1689, 2019 06 01.
Article
em En
| MEDLINE
| ID: mdl-31135049
ABSTRACT
The mechanism by which dopaminergic neurons are selectively affected in Parkinson's disease is not fully understood. In this study, we found a dramatic increase in the expression of catechol-O-methyltransferase (COMT), along with a lower level of DNA methylation, in induced pluripotent stem cell-derived dopaminergic neurons from patients with parkin (PARK2) gene mutations compared to those from healthy controls. In addition, a significant increase in the expression of COMT was found in dopaminergic neurons of isogenic PARK2 induced pluripotent stem cell lines that mimicked loss of function of PARK2 by CRISPR Cas9 technology. In dopamine transporter (DAT)-Cre mice, overexpression of COMT, specifically in dopaminergic neurons of the substantia nigra, produced cataleptic behaviours associated with impaired motor coordination. These findings suggest that upregulation of COMT, likely resulting from DNA hypomethylation, in dopaminergic neurons may contribute to the initial stage of neuronal dysfunction in Parkinson's disease.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doença de Parkinson
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Catecol O-Metiltransferase
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Ubiquitina-Proteína Ligases
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Neurônios Dopaminérgicos
Limite:
Animals
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Humans
Idioma:
En
Revista:
Brain
Ano de publicação:
2019
Tipo de documento:
Article