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Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy

Minamiyama, M.·2004·Human Molecular Genetics

Abstract

Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease caused by the expansion of a polyglutamine (polyQ) tract within the androgen receptor. Unifying mechanisms have been implicated in the pathogenesis of polyQ-dependent neurodegenerative diseases including SBMA, Huntington disease and spinocerebellar ataxias. It has been suggested that mutant protein containing polyQ inhibits histone acetyltransferase activity, resulting in transcriptional dysfunction and subsequent neuronal dysfunction. Histone deacetylase (HDAC) inhibitors alleviate neurological phenotypes in fly and mouse models of polyQ disease, although the therapeutic effect is limited by the toxicity of these compounds. We studied the therapeutic effects of sodium butyrate (SB), an HDAC inhibitor, in a transgenic mouse model of SBMA. Oral administration of SB ameliorated neurological phenotypes as well as increased acetylation of nuclear histone in neural tissues. These therapeutic effects, however, were seen only within a narrow range of SB dosage. Our results indicate that SB is a possible therapeutic agent for SBMA and other polyQ diseases, although an appropriate dose should be determined for clinical application.

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Metadata

Authors
Minamiyama, M.
Venue
Human Molecular Genetics
Published
2004-04-21
Volume
13
Issue
11
Pages
1183-1192
ISSN
  • 0964-6906 (ISSN-L)
  • 1460-2083
OpenAlex
W2096949620
Cited by
260
References
4
FWCI
6.89
Type
journal article
Language
en
Open access
closed

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CoChat. (2026). Citation check: Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. https://app.cochat.ai/papers/10.1093/hmg/ddh131
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Minamiyama, M. (2004). Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddh131

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