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Current Status of Treatment of Spinal and Bulbar Muscular Atrophy

Spinal and bulbar muscular atrophy (SBMA) is the first member identified among polyglutamine diseases characterized by slowly progressive muscle weakness and atrophy of the bulbar, facial, and limb muscles pathologically associated with motor neuron loss in the spinal cord and brainstem. Androgen re...

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Autores principales: Tanaka, Fumiaki, Katsuno, Masahisa, Banno, Haruhiko, Suzuki, Keisuke, Adachi, Hiroaki, Sobue, Gen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi Publishing Corporation 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376774/
https://www.ncbi.nlm.nih.gov/pubmed/22720173
http://dx.doi.org/10.1155/2012/369284
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author Tanaka, Fumiaki
Katsuno, Masahisa
Banno, Haruhiko
Suzuki, Keisuke
Adachi, Hiroaki
Sobue, Gen
author_facet Tanaka, Fumiaki
Katsuno, Masahisa
Banno, Haruhiko
Suzuki, Keisuke
Adachi, Hiroaki
Sobue, Gen
author_sort Tanaka, Fumiaki
collection PubMed
description Spinal and bulbar muscular atrophy (SBMA) is the first member identified among polyglutamine diseases characterized by slowly progressive muscle weakness and atrophy of the bulbar, facial, and limb muscles pathologically associated with motor neuron loss in the spinal cord and brainstem. Androgen receptor (AR), a disease-causing protein of SBMA, is a well-characterized ligand-activated transcription factor, and androgen binding induces nuclear translocation, conformational change and recruitment of coregulators for transactivation of AR target genes. Some therapeutic strategies for SBMA are based on these native functions of AR. Since ligand-induced nuclear translocation of mutant AR has been shown to be a critical step in motor neuron degeneration in SBMA, androgen deprivation therapies using leuprorelin and dutasteride have been developed and translated into clinical trials. Although the results of these trials are inconclusive, renewed clinical trials with more sophisticated design might prove the effectiveness of hormonal intervention in the near future. Furthermore, based on the normal function of AR, therapies targeted for conformational changes of AR including amino-terminal (N) and carboxy-terminal (C) (N/C) interaction and transcriptional coregulators might be promising. Other treatments targeted for mitochondrial function, ubiquitin-proteasome system (UPS), and autophagy could be applicable for all types of polyglutamine diseases.
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spelling pubmed-33767742012-06-20 Current Status of Treatment of Spinal and Bulbar Muscular Atrophy Tanaka, Fumiaki Katsuno, Masahisa Banno, Haruhiko Suzuki, Keisuke Adachi, Hiroaki Sobue, Gen Neural Plast Review Article Spinal and bulbar muscular atrophy (SBMA) is the first member identified among polyglutamine diseases characterized by slowly progressive muscle weakness and atrophy of the bulbar, facial, and limb muscles pathologically associated with motor neuron loss in the spinal cord and brainstem. Androgen receptor (AR), a disease-causing protein of SBMA, is a well-characterized ligand-activated transcription factor, and androgen binding induces nuclear translocation, conformational change and recruitment of coregulators for transactivation of AR target genes. Some therapeutic strategies for SBMA are based on these native functions of AR. Since ligand-induced nuclear translocation of mutant AR has been shown to be a critical step in motor neuron degeneration in SBMA, androgen deprivation therapies using leuprorelin and dutasteride have been developed and translated into clinical trials. Although the results of these trials are inconclusive, renewed clinical trials with more sophisticated design might prove the effectiveness of hormonal intervention in the near future. Furthermore, based on the normal function of AR, therapies targeted for conformational changes of AR including amino-terminal (N) and carboxy-terminal (C) (N/C) interaction and transcriptional coregulators might be promising. Other treatments targeted for mitochondrial function, ubiquitin-proteasome system (UPS), and autophagy could be applicable for all types of polyglutamine diseases. Hindawi Publishing Corporation 2012 2012-06-07 /pmc/articles/PMC3376774/ /pubmed/22720173 http://dx.doi.org/10.1155/2012/369284 Text en Copyright © 2012 Fumiaki Tanaka et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review Article
Tanaka, Fumiaki
Katsuno, Masahisa
Banno, Haruhiko
Suzuki, Keisuke
Adachi, Hiroaki
Sobue, Gen
Current Status of Treatment of Spinal and Bulbar Muscular Atrophy
title Current Status of Treatment of Spinal and Bulbar Muscular Atrophy
title_full Current Status of Treatment of Spinal and Bulbar Muscular Atrophy
title_fullStr Current Status of Treatment of Spinal and Bulbar Muscular Atrophy
title_full_unstemmed Current Status of Treatment of Spinal and Bulbar Muscular Atrophy
title_short Current Status of Treatment of Spinal and Bulbar Muscular Atrophy
title_sort current status of treatment of spinal and bulbar muscular atrophy
topic Review Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3376774/
https://www.ncbi.nlm.nih.gov/pubmed/22720173
http://dx.doi.org/10.1155/2012/369284
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