About: MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease

Facets (new session)
Description
Metadata
Settings
- owl:sameAs
- Inference Rule:

About: MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease
Creator	Lieberman, Andrew Jones, T Bates, P Danby, Emily Lieberman, Matthew Marchioretti, Caterina Nath, Samir Pennuto, Maria Robins, Diane Van Pelt, Kate Samuel, · Gianni Sorarù, · Gillian, · Zhigang, ·
source	Medline; PMC
abstract	Polyglutamine (polyQ) tract expansion leads to proteotoxic misfolding and drives a family of nine diseases. We study spinal and bulbar muscular atrophy (SBMA), a progressive degenerative disorder of the neuromuscular system caused by the polyQ androgen receptor (AR). Using a knock-in mouse model of SBMA, AR113Q mice, we show that E3 ubiquitin ligases which are a hallmark of the canonical muscle atrophy machinery are not induced in AR113Q muscle. Similarly, we find no evidence to suggest dysfunction of signaling pathways that trigger muscle hypertrophy or impairment of the muscle stem cell niche. Instead, we find that skeletal muscle atrophy is characterized by diminished function of the transcriptional regulator Myocyte Enhancer Factor 2 (MEF2), a regulator of myofiber homeostasis. Decreased expression of MEF2 target genes is age- and glutamine tract length-dependent, occurs due to polyQ AR proteotoxicity, and is associated with sequestration of MEF2 into intranuclear inclusions in muscle. Skeletal muscle from R6/2 mice, a model of Huntington disease which develops progressive atrophy, also sequesters MEF2 into inclusions and displays age-dependent loss of MEF2 target genes. Similarly, SBMA patient muscle shows loss of MEF2 target gene expression, and restoring MEF2 activity in AR113Q muscle rescues fiber size and MEF2-regulated gene expression. This work establishes MEF2 impairment as a novel mechanism of skeletal muscle atrophy downstream of toxic polyglutamine proteins and as a therapeutic target for muscle atrophy in these disorders. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-020-02156-4) contains supplementary material, which is available to authorized users.
has issue date	2020-04-18(xsd:dateTime)
bibo:doi	10.1007/s00401-020-02156-4
bibo:pmid	32306066
has license	no-cc
sha1sum (hex)	20060a8e218bce621675f458b5f1f5b8e33ed169
schema:url	https://doi.org/10.1007/s00401-020-02156-4
resource representing a document's title	MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease
has PubMed Central identifier	PMC7166004
has PubMed identifier	32306066
schema:publication	Acta Neuropathol
resource representing a document's body	covid:20060a8e218bce621675f458b5f1f5b8e33ed169#body_text
is schema:about of	named entity 'mechanism' named entity 'gene' named entity 'atrophy' named entity 'polyQ' named entity 'androgen' named entity 'mice' named entity 'polyQ' named entity 'muscle' named entity 'model' named entity 'muscular' named entity 'inclusions' named entity 'loss' named entity 'sequestration' named entity 'stem cell' named entity 'spinal' named entity 'leads' named entity 'glutamine' named entity 'polyQ' named entity 'intranuclear inclusions' named entity 'SBMA' named entity 'muscle' named entity 'MEF2' named entity 'Myocyte Enhancer Factor 2' named entity 'spinal and bulbar muscular atrophy' named entity 'MEF2' named entity 'muscle atrophy' named entity 'MEF2' named entity 'dysfunction' named entity 'satellite cells' named entity 'MEF2' named entity 'one-way ANOVA' named entity 'post-hoc test' named entity 'muscle biopsies' named entity 'mice' named entity 'luciferase' named entity 'CAG repeat' named entity 'glutamine' named entity 'MEF2' named entity 'E3 ubiquitin ligases' named entity 'mice' named entity 'MEF2' named entity 'atrophy' named entity 'mice' named entity 'post-translational modifications' named entity 'luciferase' named entity 'gene expression' named entity 'polyQ' named entity 'skeletal muscle' named entity 'gene expression' named entity 'coding sequence' named entity 'Myf5' named entity 'Luciferase' named entity 'atrophy' named entity 'neuron' named entity 'muscle atrophy' named entity 'quadriceps' named entity 'mice' named entity 'pathogen' named entity 'regulate the expression' named entity 'MEF2' named entity 'phenotype' named entity 'Redd1' named entity 'gain of function' named entity 'MEF2' named entity 'hormone' named entity 'Mef2c' named entity 'PBS' named entity 'Redd1'

Faceted Search & Find service v1.13.91 as of Mar 24 2020

Alternative Linked Data Documents: Sponger | ODE Content Formats:

RDF

ODATA

Microdata

About

OpenLink Virtuoso version 07.20.3229 as of Jul 10 2020, on Linux (x86_64-pc-linux-gnu), Single-Server Edition (94 GB total memory)
Data on this page belongs to its respective rights holders.
Virtuoso Faceted Browser Copyright © 2009-2025 OpenLink Software