Transcriptional signature of an altered purine metabolism in the skeletal muscle of a Huntington’s disease mouse model

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Title: Transcriptional signature of an altered purine metabolism in the skeletal muscle of a Huntington’s disease mouse model
Author(s): Mielcarek, M
Smolenski, RT
Isalan, M
Item Type: Journal Article
Abstract: Huntington’s disease (HD) is a fatal neurodegenerative disorder, caused by a polyglutamine expansion in the huntingtin protein (HTT). HD has a peripheral component to its pathology: skeletal muscles are severely affected, leading to atrophy and malfunction in both pre-clinical and clinical settings. We previously used two symptomatic HD mouse models to demonstrate the impairment of the contractile characteristics of the hind limb muscles, which was accompanied by a significant loss of function of motor units. The mice displayed a significant reduction in muscle force, likely because of deteriorations in energy metabolism, decreased oxidation and altered purine metabolism. There is growing evidence suggesting that HD-related skeletal muscle malfunction might be partially or completely independent of CNS degeneration. The pathology might arise from mutant HTT within muscle (loss or gain of function). Hence, it is vital to identify novel peripheral biomarkers that will reflect HD skeletal muscle atrophy. These will be important for upcoming clinical trials that may target HD peripherally. In order to identify potential biomarkers that might reflect muscle metabolic changes, we used qPCR to validate key gene transcripts in different skeletal muscle types. Consequently, we report a number of transcript alterations that are linked to HD muscle pathology.
Publication Date: 31-Dec-2017
Date of Acceptance: 17-Feb-2017
DOI: 10.3389/fphys.2017.00127
ISSN: 1664-042X
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Physiology
Copyright Statement: This paper is embargoed until publication. Once published will be available fully open access.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MC_PC15028
Keywords: Huntington's disease
mouse models
purine metabolism
skeletal muscle atrophy
transcriptional deregulation
Publication Status: Accepted
Embargo Date: publication subject to indefinite embargo
Open Access location:
Appears in Collections:Faculty of Natural Sciences

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