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10.1007/s00401-020-02156-4 http://scihub22266oqcxt.onion/10.1007/s00401-020-02156-4 32306066!7166004!32306066     free     free     free Warning: file_get_contents(https://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=32306066&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 215 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Warning: imagejpeg(C:\Inetpub\vhosts\kidney.de\httpdocs\phplern\32306066.jpg): Failed to open stream: No such file or directory in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 117       Acta+Neuropathol 2020 ; 140 (1): 63-80 Nephropedia Template TP {{tp|p=32306066|t=2020. MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease |pdf=|usr=}}{{32306066}} gab.com Text MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease JO: Acta Neuropathol http://www.kidney.de/pget.php?&tw=1&pmid=32306066 #FOAvip 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. Twit Text FOAVip MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease ????Acta Neuropathol http://www.kidney.de/pget.php?&tw=1&pmid=32306066 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=32306066 #FOAvip English Wikipedia <ref>{{Cite pmid|32306066}}</ref> MEF2 impairment underlies skeletal muscle atrophy in polyglutamine disease #MMPMID32306066 Nath SR; Lieberman ML; Yu Z; Marchioretti C; Jones ST; Danby ECE; Van Pelt KM; Soraru G; Robins DM; Bates GP; Pennuto M; Lieberman AP Acta Neuropathol 2020[Jul]; 140 (1): 63-80 PMID32306066show ga 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. |Animals[MESH] |Bulbo-Spinal Atrophy, X-Linked/*metabolism/*pathology[MESH] |Humans[MESH] |Huntington Disease/metabolism/pathology[MESH] |MEF2 Transcription Factors/*metabolism[MESH] |Mice[MESH] |Muscle, Skeletal/metabolism/pathology[MESH] |Muscular Atrophy/*metabolism/*pathology[MESH]MEF2 impairment underlies skeletal muscle atrophy in polyglutamine dis(epmc).pdf DeepDyve Pubget Overpricing