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: 2-Mar-2017
Date of Acceptance: 17-Feb-2017
ISSN: 1664-042X
Publisher: Frontiers Media
Journal / Book Title: Frontiers in Physiology
Volume: 8
Copyright Statement: © 2017 Mielcarek, Smolenski and Isalan. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
Sponsor/Funder: Medical Research Council (MRC)
Funder's Grant Number: MC_PC15028
Keywords: Science & Technology
Life Sciences & Biomedicine
Huntington's disease
skeletal muscle atrophy
purine metabolism
transcriptional deregulation
mouse models
Huntington's disease
mouse models
purine metabolism
skeletal muscle atrophy
transcriptional deregulation
Publication Status: Published
Article Number: 127
Open Access location:
Appears in Collections:Faculty of Natural Sciences

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