Dysregulated COMT expression in fragile X syndrome

Utami, Kagistia Hana, Yusof, Nur Amirah Binte Muhammed, Garcia-Miralles, Marta, Skotte, Niels Henning, Nama, Srikanth, Sampath, Prabha, Langley, Sarah R. ORCID: https://orcid.org/0000-0003-4419-476X and Pouladi, Mahmoud A. 2023. Dysregulated COMT expression in fragile X syndrome. NeuroMolecular Medicine 25 (4) , pp. 644-649. 10.1007/s12017-023-08754-1

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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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences
Publisher:	Springer
ISSN:	1535-1084
Date of First Compliant Deposit:	24 October 2023
Date of Acceptance:	20 August 2023
Last Modified:	08 Nov 2024 14:45
URI:	https://orca.cardiff.ac.uk/id/eprint/163150

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