専門 : 神経薬理化学 (Neurochemical Pharmacology)

研究テーマ

１． パーキンソン病などの神経変性疾患モデルの病態解析とその保護・修復（Study on pathophysiology and neuroprotection for neurodegenerative diseases）
       新しい治療法の開発（Development of novel therapeutic strategies)

２． 神経疾患の治療標的としてのアストロサイトの役割の解明（Study on role of astrocyte as a neurotherapeutic target）

３． 乱用薬物（覚醒剤，違法ドラッグ）の神経毒性と防御（Neurotoxicity of drugs abused (methamphetamine, illegal drugs)）

研究キーワード

パーキンソン病 (Parkinson's disease)
変性疾患（neurodegenerative disease )
ドーパミン (dopamine)
酸化ストレス (oxidative stress)
覚せい剤 メタンフェタミン(methaphetamine)
グリア細胞 (glia)

主な研究業績

Miyazaki, I., Asanuma, M., Murakami, S., Takeshima, M., Torigoe, N., Kitamura, Y. and Miyoshi, K.: Targeting 5-HT1A receptors in astrocytes to protect dopaminergic neurons in parkinsonian models. 　Neurobiol. Dis.,  59: 244-256, 2013.

Asanuma, M., Miyazaki, I., Murakami, S., Diaz-Corrales, F.J. and Ogawa, N.: Striatal astrocytes act as a reservoir for L-DOPA. PLoS ONE, 9(9): e106362, 2014. doi:10.1371/journal.pone.0106362.

Murakami, S., Miyazaki, I., Sogawa, N.*, Miyoshi, K.*, Asanuma, M.:Neuroprotective effects of metallothionein against rotenone-induced myenteric neurodegeneration in Parkinsonian mice.  Neurotox. Res., 26: 285-98, 2014. DOI10.1007/s12640-014-9480-1.

Asanuma, M., Miyazaki, I., Diaz-Corrales, F.J.*, Higashi, Y.*, Namba, M.* and Ogawa, N.: Transplantation of melanocytes obtained from the skin ameliorates apomorphine-induced abnormal behavior in rodent hemi-parkinsonian models.  PLoS ONE, 8(6): e65983, 2013. doi:10.1371/journal.pone.0065983.

Diaz-Corrales, F.J., Miyazaki, I., Asanuma, M., Ruano, D.* and Rios, R.M.*: Centrosomal aggregates and Golgi fragmentation disrupt vesicular trafficking of DAT. Neurobiol. Aging, 33:2462-2477, 2012.

Asanuma, M., Miyazaki, I., Kikkawa, Y., Kimoto, N., Takeshima, M., Murakami, S., Miyoshi, K.: Cyclooxygenase-independent neuroprotective effects of aspir against dopamine quinone-induced neurotoxicity. Neurochem. Res., 37: 1944-1951, 2012.

Miyazaki, I., Asanuma, M., Kikkawa, Y., Takeshima, M., Murakami, S., Miyoshi, K., Sogawa, N. and Kita, T.: Astrocyte-derived metallothionein protects dopaminergic neurons from dopamine quinone toxicity. Glia, 59: 435-451, 2011.

Takeshima, M., Murata, M.*, Urasoe, N.*, Murakami, S, Miyazaki, I., Asanuma, M. and Kita, T.*: Protective effects of baicalein against excess L-DOPA-induced dopamine quinone neurotoxicity. Neurol. Res., 33: 1050-1056, 2011.

Ogawa, D., Asanuma, M., Miyazaki, I., Tachibana, H.*, Wada, J.*, Sogawa, N.*, Sugaya, T.*, Kitamura, S.*, Maeshima, Y.*, Shikata, K.* and Makino, F.*:High glucose increases metallothionein expression in renal proximal tubular epithelial cells. Exp. Diabetes Res., i 2011: 534872, 2011.

Asanuma, M., Miyazaki, I., Diaz-Corrales, F.J., Kimoto, N., Kikkawa, Y., Takeshima, M., Miyoshi, K. and Murata, M.*: Neuroprotective effects of zonisamide target astrocyte. Ann. Neurol., 67:239-249, 2010.

Miyazaki, I., and Asanuma M.: Antioxidative andneuroprotective effects of metallothioneins on dopaminergic neurons. Handbook of Free Radicals: Formation, Types and Effects (Kozyrev, D., Slutsky, V., ed), Nova Science Publishers, pp.557-568, 2010.

Miyazaki, I. and Asanuma, M. Approaches to prevent dopamine quinone- induced neurotoxicity. Neurochem. Res., 34: 698-706, 2009.

Tsuji, T.,Asanuma, M., Miyazaki, I., Miyoshi, K. and Ogawa, N.: Reduction of nuclear peroxisome proliferator-activated receptor γ expression in methamphetamine-induced neurotoxicity and neuroprotective effects of ibuprofen. Neurochem. Res., 34:764-774, 2009.

Miyoshi, K., Kasahara, K., Miyazaki, I., Shimizu, S.*, Taniguchi, M.*, Matsuzaki, S.*, Tohyama, M.*, Asanuma, M.: Pericentrin, a centrosomal protein related to microcephalic primordial dwarfism, is required for olfactory cilia assembly in mice. FASEB J., 23: 3289-3297, 2009.

Miyoshi K, Kasahara K, Miyazaki I, Asanuma M.: Lithium treatment elongates primary cilia in the mouse brain and in cultured cells. Biochem. Biophys. Res. Commun., 388 757-762, 2009.

Asanuma, M., Miyazaki, I., Diaz-Corrales, F.J., Miyoshi, K., Ogawa, N. and Murata, M.: Preventing effects of a novel anti-parkinsonian agent zonisamide on dopamine quinone formation. Neurosci. Res., 60: 106-113, 2008.

Hozumi, H., Asanuma, M., Miyazaki, I., Fukuoka, S., Kikkawa, Y., Kimoto, N., Kitamura, Y., Sendo, T., Kita, T. and Gomita, Y.: Protective effects of interferon-gamma against methamphetamine-induced neurotoxicity. Toxicol. Lett., 177: 123-129, 2008.

Shimizu, M., Miyazaki, I., Higashi, Y., Eslava-Alva, M.J., Diaz-Corrales, F.J., Asanuma, M. and Ogawa, N.: Specific induction of PAG608 in cranial and spinal motor neurons of L-DOPA-treated parkinsonian rats. Neurosci. Res., 60: 355-363, 2008.

Díaz-Corrales, F.J., Asanuma, M., Miyazaki, I., Miyoshi, K., Hattori, N.* and Ogawa, N. :Dopamine induces supernumerary centrosomes and subsequent cell death through Cdk2 up-regulation in dopaminergic neuronal cells. Neurotox. Res., 14: 295-305, 2008.

Miyazaki, I., Asanuma, M., Hozumi, H., Miyoshi, K. and Sogawa, N.: Protective effects of metallothionein against dopamine quinone-induced dopaminergic neurotoxicity. FEBS. Lett., 581: 5003-5008, 2007.

Asanuma, M. and Miyazaki, I.: Common anti-inflammatory drugs are potentially therapeutic for Parkinson's disease? Exp. Neurol., 206: 172-178, 2007.

Miyoshi, K., Asanuma, M., Miyazaki, I., Matsuzaki, S., Tohyama, M. and Ogawa, N.: Characterization of pericentrin isoforms in vivo. Biochem. Biophys. Res. Commun., 351: 745-749, 2006.

Miyazaki, I., Asanuma, M., Diaz-Corrales, F.J., Fukuda, M., Kitaichi, K., Miyoshi, K. and Ogawa, N.: Methamphetamine-induced dopaminergic neurotoxicity is regulated by quinone formation-related molecules. FASEB J., 20: 571-573, 2006 (published online January 10, 2006).

Miyazaki, I., Asanuma, M., Diaz-Corrales, F.J., Miyoshi, K. and Ogawa, N.: Dopamine agonist pergolide prevents levodopa-induced quinoprotein formation in parkinsonian striatum and shows quenching effects on dopamine-semiquinone generated in vitro. Clin. Neuropharmacol., 28: 155-160, 2005.

Diaz-Corrales, F.J., Asanuma, M., Miyazaki, I., Miyoshi, K. and Ogawa, N.: Rotenone induces aggregation of gamma-tubulin protein and subsequent disorganization of the centrosome: Relevance to formation of inclusion bodies and neurodegeneration. Neuroscience, 133: 117-135, 2005.

Miyazaki, I., Asanuma, M., Diaz-Corrales, F.J., Miyoshi, K. and Ogawa, N.: Direct evidence for expression of dopamine receptors in astrocytes from basal ganglia. Brain Res., 1029: 120-123, 2004.

Higashi, Y., Asanuma, M., Miyazaki, I., Hattori, N., Mizuno, Y. and Ogawa, N.: Parkin attenuates manganese-induced dopaminergic cell death. J. Neurochem., 89: 1490-1497, 2004.

Miyoshi, K., Asanuma, M., Miyazaki, I., Diaz-Corrales, F. J., Katayama, T., Tohyama, M. and Ogawa, N.: DISC1 localizes to the centrosome by binding to kendrin. Biochem. Biophys. Res. Commun., 317: 1195-1199, 2004.

Asanuma, M., Miyazaki, I. and Ogawa, N.: Dopamine- or L-DOPA-induced neurotoxicity: the role of dopamine quinone formation and tyrosinase in a model of Parkinson's disease. Neurotox. Res., 5: 165-176, 2003.

Haque, M.E., Asanuma, M., Higashi, Y., Miyazaki, I., Tanaka, K. and Ogawa, N.: Apoptosis-inducing neurotoxicity of dopamine and its metabolites via reactive quinone generation in neuroblastoma cells. Biochim. Biophys. Acta, 1619: 39-52, 2003.

Higashi, Y., Asanuma, M., Miyazaki, I., Haque, M.E., Fujita, N., Tanaka, K. and Ogawa, N.: The p53-activated gene, PAG608, requires a zinc finger domain for nuclear localization and oxidative stress-induced apoptosis. J. Biol. Chem., 277: 42224-42232, 2002.

Asanuma, M., Nishibayashi-Asanuma, S., Miyazaki, I., Kohno, M. and Ogawa, N.: Neuroprotective effects of non-steroidal anti-inflammatory drugs by direct scavenging of nitric oxide radicals. J. Neurochem., 76: 1895-1904, 2001.

Higashi, Y., Asanuma, M., Miyazaki, I. and Ogawa, N.: Inhibition of tyrosinase reduces cell viability in catecholaminergic neuronal cells. J. Neurochem., 75: 1771-1774, 2000.

Asanuma, M., Hayashi, T., Ordonez, S.V., Ogawa, N. and Cadet, J.L.: Direct interactions of methamphetamine with the nucleus. Mol. Brain Res., 80: 237-243, 2000.

Iwata-Ichikawa, E., Kondo, Y., Miyazaki, I., Asanuma, M. and Ogawa, N.: Glial cells protect neurons against oxidative stress via transcriptional up-regulation of the glutathione synthesis. J. Neurochem., 72: 2334-2344, 1999.

Asanuma, M. and Cadet, J.L.: Methamphetamine-induced increase in striatal NF-kB DNA-binding activity is attenuated in superoxide dismutase transgenic mice. Mol. Brain Res., 60: 305-309, 1998.

Gomez-Vargas, M., Nishibayashi-Asanuma, S., Asanuma, M., Kondo, Y., Iwata, E. and Ogawa, N.: Pergolide scavenges both hydroxyl and nitric oxide free radicals in vitro and inhibits lipid peroxidation in different regions of the rat brain. Barin Res., 790: 202-208, 1998.

Asanuma, M., Hirata, H. and Cadet, J.L.: Attenuation of 6-hydroxydopamine-induced dopaminergic nigrostriatal lesions in superoxide dismutase transgenic mice. Neuroscience, 85: 907-917, 1998.

Asahara, H., Fujisawa, K., Kobata, T., Hasunuma, T., Maeda, T., Asanuma, M., Ogawa, N., Inoue, H., Sumida, T. and Nishioka, K.: Direct evidence of high DNA-binding activity of transcription factor AP-1 in the synovium with rheumatoid arthritis. Arthritis Rheum., 40: 912-918, 1997.

Nishibayashi, S., Asanuma, M., Kohno, M., Gomez-Vargas, M. and Ogawa, N.: Scavenging effects of dopamine agonists on nitric oxide radicals. J. Neurochem., 67: 2208-2211, 1996.

Asanuma, M., Nishibayashi, S., Kondo, Y., Iwata, E., Tsuda, M. and Ogawa, N.: Effects of single cyclosporin A pretreatment on pentylenetetrazol-induced convulsion and on TRE-binding activity in the rat brain. Mol. Brain Res., 33: 29-36, 1995.

Asanuma, M., Ogawa, N., Nishibayashi, S., Kawai, M., Kondo, Y. and Iwata, E.: Protective effects of pergolide on dopamine levels in the 6-hydroxydopamine-lesioned mouse brain. Arch. Int. Pharmacodyn. Ther., 329: 221-230, 1995.

Kondo, Y., Ogawa, N., Asanuma, M., Ota, Z. and Mori, A.: Regional differences in late onset iron deposition, ferritin, transferrin, astrocyte proliferation and microglial activation after transient forebrain ischemia in rat brain. J. Cereb. Blood Flow Metab., 15: 216-226, 1995.

Ogawa, N., Tanaka, K., Asanuma, M., Kawai, M., Masumizu, T., Kohno, M. and Mori, A.: Bromocriptine protects mice against 6-hydroxydopamine and scavenges hydroxyl free radicals in vitro. Brain Res., 657: 207-213, 1994.

Ogawa, N., Asanuma, M., Kondo, Y., Kawada, Y. and Mori, A.: Differential effects of chronic L-DOPA treatment on lipid peroxidation in the mouse brain with or without pretreatment with 6-hydroxydopamine. Neurosci. Lett., 171: 55-58, 1994.

Asanuma, M., Ogawa, N., Haba, K., Hirata, H. and Mori, A.: Effects of chronic catecholamine depletions on muscarinic M1-receptor and its mRNA in rat brain. J. Neurol. Sci., 110: 205-214, 1992.

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