| RRC ID |
2395
|
| Author |
Minamiyama M, Katsuno M, Adachi H, Waza M, Sang C, Kobayashi Y, Tanaka F, Doyu M, Inukai A, Sobue G.
|
| Title |
Sodium butyrate ameliorates phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy.
|
| Journal |
Hum Mol Genet
|
| 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.
|
| Volume |
13(11)
|
| Pages |
1183-92
|
| Published |
2004-6-1
|
| DOI |
10.1093/hmg/ddh131
|
| PII |
ddh131
|
| PMID |
15102712
|
| MeSH |
Acetylation
Administration, Oral
Animals
Butyrates / administration & dosage
Butyrates / therapeutic use*
Dose-Response Relationship, Drug
Enzyme Inhibitors / administration & dosage
Enzyme Inhibitors / therapeutic use*
Gait Ataxia / drug therapy
Histone Deacetylase Inhibitors*
Histones / metabolism
Intranuclear Inclusion Bodies / drug effects
Mice
Mice, Transgenic
Motor Neurons / metabolism
Muscles / pathology
Muscular Disorders, Atrophic / drug therapy*
Muscular Disorders, Atrophic / metabolism
Muscular Disorders, Atrophic / pathology
Neuroglia / metabolism
Receptors, Androgen / metabolism
Rotarod Performance Test
Spinal Cord / pathology
Spinal Nerve Roots / pathology
Survival Analysis
|
| IF |
5.101
|
| Times Cited |
184
|
|
WOS Category
|
GENETICS & HEREDITY
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Mice |
RBRC00344
RBRC00373 |
