研究者詳細 - 勝野　雅央

論文 - 勝野　雅央

分割表示 499 件中 481 - 499 件目／全件表示 >>

Gene Expression Profiling toward Understanding of ALS Pathogenesis. 招待有り査読有り

Tanaka F, Niwa J, Ishigaki S, Katsuno M, Waza M, Yamamoto M, Doyu M, Sobue G.

Ann N Y Acad Sci 1086 巻頁： 1-10 2006年

Alleviating Neurodegeneration by an Anticancer Agent: An Hsp90 Inhibitor (17-AAG). 招待有り査読有り

Waza M, Adachi H, Katsuno M, Minamiyama M, Tanaka F, Sobue G.

Ann N Y Acad Sci 1086 巻頁： 21-34 2006年

Reversible disruption of dynactin 1-mediated retrograde axonal transport in polyglutamine-induced motor neuron degeneration. 査読有り

Katsuno M, Adachi H, Minamiyama M, Waza M, Tokui K, Banno H, Suzuki K, Onoda Y, Tanaka F, Doyu M, Sobue G.

J Neurosci 26 巻頁： 12106-12117 2006年

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

Spinal and bulbar muscular atrophy (SBMA) is a hereditary neurodegenerative disease caused by an expansion of a trinucleotide CAG repeat encoding the polyglutamine tract in the androgen receptor (AR) gene. To elucidate the pathogenesis of polyglutamine-mediated motor neuron dysfunction, we investigated histopathological and biological alterations in a transgenic mouse model of SBMA carrying human pathogenic AR. In affected mice, neurofilaments and synaptophysin accumulated at the distal motor axon. A similar intramuscular accumulation of neurofilament was detected in the skeletal muscle of SBMA patients. Fluoro-gold labeling and sciatic nerve ligation demonstrated an impaired retrograde axonal transport in the transgenic mice. The mRNA level of dynactin 1, an axon motor for retrograde transport, was significantly reduced in the SBMA mice resulting from pathogenic AR-induced transcriptional dysregulation. These pathological events were observed before the onset of neurological symptoms, but were reversed by castration, which prevents nuclear accumulation of pathogenic AR. Overexpression of dynactin 1 mitigated neuronal toxicity of the pathogenic AR in a cell culture model of SBMA. These observations indicate that polyglutamine-dependent transcriptional dysregulation of dynactin 1 plays a crucial role in the reversible neuronal dysfunction in the early stage of SBMA.

Mutant androgen receptor accumulation in spinal and bulbar muscular atrophy scrotal skin: a pathogenic marker. 査読有り

Banno H, Adachi H, Katsuno M, Suzuki K, Atsuta N, Watanabe H, Tanaka F, Doyu M, Sobue G.

Ann Neurol 59 巻頁： 520-526 2006年

Natural history of spinal and bulbar muscular atrophy (SBMA): a study of 223 Japanese patients. 査読有り

Atsuta N, Watanabe H, Ito M, Banno H, Suzuki K, Katsuno M, Tanaka F, Tamakoshi A, Sobue G.

Brain 129 巻頁： 1446-1455 2006年

Pathogenesis, animal models and therapeutics in Spinal and Bulbar Muscular Atrophy (SBMA). 招待有り査読有り

Katsuno M, Adachi H, Waza M, Banno H, Suzuki K, Tanaka F, Doyu M, Sobue G.

Exp Neurol 200 巻頁： 8-18 2006年

Clinicopathologic features of nonsystemic vasculitic neuropathy and microscopic polyangiitis-associated neuropathy: A comparative study. 査読有り

Sugiura M, Koike H, Iijima M, Mori K, Hattori N, Katsuno M, Tanaka F, Sobue G.

J Neurol Sci 241 巻頁： 31-37 2006年

Widespread nuclear and cytoplasmic accumulation of mutant androgen receptor in SBMA patients. 査読有り

Adachi H, Katsuno M, Minamiyama M, Waza M, Sang C, Nakagomi Y, Kobayashi Y, Tanaka F, Doyu M, Inukai A, Yoshida M, Hashizume Y, Sobue G.

Brain 128 巻頁： 659-670 2005年

Pharmacological induction of heat-shock proteins alleviates polyglutamine-mediated motor neuron disease. 査読有り

Katsuno M, Sang C, Adachi H, Minamiyama M, Waza M, Tanaka F, Doyu M, Sobue G.

Proc Natl Acad Sci USA 102 巻頁： 16801-16806 2005年

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

Spinal and bulbar muscular atrophy (SBMA) is an adult-onset motor neuron disease caused by the expansion of a trinucleotide CAG repeat encoding the polyglutamine tract in the first exon of the androgen receptor gene (AR). The pathogenic, polyglutamine-expanded AR protein accumulates in the cell nucleus in a ligand-dependent manner and inhibits transcription by interfering with transcriptional factors and coactivators. Heat-shock proteins (HSPs) are stress-induced chaperones that facilitate the refolding and, thus, the degradation of abnormal proteins. Geranylgeranylacetone (GGA), a nontoxic antiulcer drug, has been shown to potently induce HSP expression in various tissues, including the central nervous system. In a cell model of SBMA, GGA increased the levels of Hsp70, Hsp90, and Hsp105 and inhibited cell death and the accumulation of pathogenic AR. Oral administration of GGA also up-regulated the expression of HSPs in the central nervous system of SBMA-transgenic mice and suppressed nuclear accumulation of the pathogenic AR protein, resulting in amelioration of polyglutamine-dependent neuromuscular phenotypes. These observations suggest that, although a high dose appears to be needed for clinical effects, oral GGA administration is a safe and promising therapeutic candidate for polyglutamine-mediated neurodegenerative diseases, including SBMA.

17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration. 査読有り

Waza M, Adachi H, Katsuno M, Minamiyama M, Sang C, Tanaka F, Inukai A, Doyu M, Sobue G.

Nat Med 11 巻頁： 1088-1095 2005年

記述言語：英語掲載種別：研究論文（学術雑誌）

Heat-shock protein 90 (Hsp90) functions as part of a multichaperone complex that folds, activates and assembles its client proteins. Androgen receptor (AR), a pathogenic gene product in spinal and bulbar muscular atrophy (SBMA), is one of the Hsp90 client proteins. We examined the therapeutic effects of 17-allylamino-17-demethoxygeldanamycin (17-AAG), a potent Hsp90 inhibitor, and its ability to degrade polyglutamine-expanded mutant AR. Administration of 17-AAG markedly ameliorated motor impairments in the SBMA transgenic mouse model without detectable toxicity, by reducing amounts of monomeric and aggregated mutant AR. The mutant AR showed a higher affinity for Hsp90-p23 and preferentially formed an Hsp90 chaperone complex as compared to wild-type AR; mutant AR was preferentially degraded in the presence of 17-AAG in both cells and transgenic mice as compared to wild-type AR. 17-AAG also mildly induced Hsp70 and Hsp40. 17-AAG would thus provide a new therapeutic approach to SBMA and probably to other related neurodegenerative diseases.

The wide spectrum of clinical manifestations in Sjogren's syndrome-associated neuropathy. 査読有り

Mori K, Iijima M, Koike H, Hattori N, Tanaka F, Watanabe H, Katsuno M, Fujita A, Aiba I, Ogata A, Saito T, Asakura K, Yoshida M, Hirayama M, Sobue G.

Brain 128 巻頁： 2518-2534 2005年

Geranylgeranylacetone ameliorates ischemic acute renal failure via induction of Hsp70. 査読有り

Suzuki S, Maruyama S, Sato W, Morita Y, Sato F, Miki Y, Kato S, Katsuno M, Sobue G, Yuzawa Y, Matsuo S.

Kidney Int 67 巻頁： 2210-2220 2005年

Clinical and electrophysiologic correlates of IVIg responsiveness in CIDP. 査読有り

Iijima M, Yamamoto M, Hirayama M, Tanaka F, Katsuno M, Mori K, Koike H, Hattori N, Arimura K, Nakagawa M, Yoshikawa H, Hayasaka K, Onodera O, Baba M, Yasuda H, Saito T, Nakazato M, Nakashima K, Kira J, Kaji R, Oka N, Sobue G.

Neurology 64 巻頁： 1471-1475 2005年

Gene expression profile of spinal motor neurons in sporadic amyotrophic lateral sclerosis. 査読有り

Jiang YM, Yamamoto M, Kobayashi Y, Yoshihara T, Liang Y, Terao S, Takeuchi H, Ishigaki S, Katsuno M, Adachi H, Niwa J, Tanaka F, Doyu M, Yoshida M, Hashizume Y, Sobue G.

Ann Neurol 57 巻頁： 236-251 2005年

Multiple regional 1H-MR spectroscopy in multiple system atrophy: NAA/Cr reduction in pontine base as a valuable diagnostic marker. 査読有り

Watanabe H, Fukatsu H, Katsuno M, Sugiura M, Hamada K, Okada Y, Hirayama M, Ishigaki T, Sobue G.

J Neurol Neurosurg Psychiatry 75 巻頁： 103-109 2004年

Polyglutamine diminishes VEGF; passage to motor neuron death? 招待有り査読有り

Katsuno M, Sobue G.

Neuron 41 巻頁： 677-679 2004年

Sweet relief for Huntington disease. 招待有り査読有り

Katsuno M, Adachi H, Sobue G.

Nat Med 10 巻頁： 123-124 2004年

Spinal and bulbar muscular atrophy: ligand-dependent pathogenesis and therapeutic perspectives. 招待有り査読有り

Katsuno M, Adachi H, Tanaka F, Sobue G.

J Mol Med 82 巻頁： 298-307 2004年

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

Minamiyama M, Katsuno M, Adachi H, Waza M, Sang C, Kobayashi Y, Tanaka F, Doyu M, Inukai A, Sobue G.

Hum Mol Genet 13 巻頁： 1183-92 2004年

記述言語：英語掲載種別：研究論文（学術雑誌）

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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