Journal Article

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

Makoto Minamiyama, Masahisa Katsuno, Hiroaki Adachi, Masahiro Waza, Chen Sang, Yasushi Kobayashi, Fumiaki Tanaka, Manabu Doyu, Akira Inukai and Gen Sobue

in Human Molecular Genetics

Volume 13, issue 11, pages 1183-1192
Published in print June 2004 | ISSN: 0964-6906
Published online April 2004 | e-ISSN: 1460-2083 | DOI: http://dx.doi.org/10.1093/hmg/ddh131
Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy

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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.

Journal Article.  5887 words.  Illustrated.

Subjects: Genetics and Genomics

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