Dysregulated COMT Expression in Fragile X Syndrome.
Neuromolecular Med
; 25(4): 644-649, 2023 Dec.
Article
em En
| MEDLINE
| ID: mdl-37684514
ABSTRACT
Transcriptional and proteomics analyses in human fragile X syndrome (FXS) neurons identified markedly reduced expression of COMT, a key enzyme involved in the metabolism of catecholamines, including dopamine, epinephrine and norepinephrine. FXS is the most common genetic cause of intellectual disability and autism spectrum disorders. COMT encodes for catechol-o-methyltransferase and its association with neuropsychiatric disorders and cognitive function has been extensively studied. We observed a significantly reduced level of COMT in in FXS human neural progenitors and neurons, as well as hippocampal neurons from Fmr1 null mice. We show that deficits in COMT were associated with an altered response in an assay of dopaminergic activity in Fmr1 null mice. These findings demonstrate that loss of FMRP downregulates COMT expression and affects dopamine signaling in FXS, and supports the notion that targeting catecholamine metabolism may be useful in regulating certain neuropsychiatric aspects of FXS.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Catecol O-Metiltransferase
/
Síndrome do Cromossomo X Frágil
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Neuromolecular Med
Assunto da revista:
BIOLOGIA MOLECULAR
/
NEUROLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
Singapura