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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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2012-01-01
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| Series: | Neural Plasticity |
| Online Access: | http://dx.doi.org/10.1155/2012/369284 |
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| author | Fumiaki Tanaka Masahisa Katsuno Haruhiko Banno Keisuke Suzuki Hiroaki Adachi Gen Sobue |
| author_facet | Fumiaki Tanaka Masahisa Katsuno Haruhiko Banno Keisuke Suzuki Hiroaki Adachi Gen Sobue |
| author_sort | Fumiaki Tanaka |
| collection | DOAJ |
| 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. |
| format | Article |
| id | doaj-art-eb5fb181d91c4e3189c4c491d60d93bb |
| institution | Kabale University |
| issn | 2090-5904 1687-5443 |
| language | English |
| publishDate | 2012-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Neural Plasticity |
| spelling | doaj-art-eb5fb181d91c4e3189c4c491d60d93bb2025-02-03T01:26:15ZengWileyNeural Plasticity2090-59041687-54432012-01-01201210.1155/2012/369284369284Current Status of Treatment of Spinal and Bulbar Muscular AtrophyFumiaki Tanaka0Masahisa Katsuno1Haruhiko Banno2Keisuke Suzuki3Hiroaki Adachi4Gen Sobue5Department of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanDepartment of Neurology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550, JapanSpinal 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.http://dx.doi.org/10.1155/2012/369284 |
| spellingShingle | Fumiaki Tanaka Masahisa Katsuno Haruhiko Banno Keisuke Suzuki Hiroaki Adachi Gen Sobue Current Status of Treatment of Spinal and Bulbar Muscular Atrophy Neural Plasticity |
| 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 |
| url | http://dx.doi.org/10.1155/2012/369284 |
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