目次
専門
神経薬理化学 神経保護・修復
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 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 ３．食品中に溶出しうる内分泌撹乱物質の母胎への暴露が産児脳発達に及ぼす影響 ４．一次繊毛の神経伝達・神経病態における役割の解明 ５．乱用薬物（覚醒剤、危険ドラッグ）の神経毒性と防御
研究キーワード
パーキンソン病; ドパミン; グリア細胞; 酸化ストレス; 脳発達; キノン体 ; 乱用薬物
主な業績
Asanuma, M. and Miyazaki, I.: Glutathione and related molecules in parkinsonism. Int. J. Mol. Sci., 22(16), 8689, 2021. doi: 10.3390/ijms22168689 Miyazaki, I. and Asanuma, M.: Neuron-astrocyte interactions in Parkinson’s disease. Cells, 9: 2623, 2020. Kikuoka, R., Miyazaki, I., Kubota, N., Maeda, M., Kagawa, D., Moriyama, M., Sato, A., Murakami, S., Kitamura, Y., Sendo, T. and Asanuma, M.: Mirtazapine exerts astrocyte-mediated dopaminergic neuroprotection. Sci. Rep., 10: 20698, 2020. Miyazaki, I. and Asanuma, M.: The rotenone models reproducing central and peripheral features of Parkinson's disease. NeuroSci., 1(1): 1-14, 2020. Miyazaki, I., Isooka, N., Imafuku, F., Sun, J., Kikuoka, R., Furukawa, C. and Asanuma, M.: Chronic systemic exposure to low-dose rotenone induced central and peripheral neuropathology and motor deficits in mice: Reproducible animal model of Parkinson's disease. Int. J. Mol. Sci., 21(9): 3254, 2020. Miyazaki, I., Kikuoka, R., Isooka, N., Takeshima, M., Sonobe, K., Arai, R., Funakoshi, H., Quin, K., Smart, J., Zensho, K. and Asanuma, M.: Effects of maternal bisphenol A diglycidyl ether exposure during gestation and lactation on behavior and brain development of the offspring. Food and Chemical Toxicol., 138: 111235, 2020. Asanuma, M., Miyazaki, I. and Funada, M.: The neurotoxicity of psychoactive phenethylamines "2C series" in cultured monoaminergic neuronal cell lines. Forensic Toxicol., 38: 394–408, 2020. Isooka, N., Miyazaki, I., Kikuoka, R., Wada, K., Nakayama, E., Shin, K., Yamamoto, D., Kitamura, Y. and Asanuma, M.: Dopaminergic neuroprotective effects of rotigotine via 5-HT1A receptors: possibly involvement of metallothionein expression in astrocytes. Neurochem. Int., 132: 104608, 2020. Asanuma, M., Okumura-Torigoe, N., Miyazaki, I., Murakami, S., Kitamura, Y. and Sendo, T.: Region-specific neuroprotective features of astrocytes against oxidative stress induced by 6-hydroxydopamine. Int. J. Mol. Sci., 20(3): 598, 2019. Miyazaki, I., Isooka, N., Wada, K., Kikuoka, R., Kitamura, Y., and Asanuma, M.: Effects of enteric environmental modification by coffee components on neurodegeneration in rotenone-treated mice. Cells, 8(3): pii: E221, 2019. Miyazaki, I. and Asanuma, M.: Therapeutic strategy of targeting astrocytes for neuroprotection in Parkinson's disease. Curr. Pharm. Des., 23(33): 4936-4947, 2017. Miyazaki, I., Murakami, S., Nakano, T., Torigoe, N., Kikuoka, R., Kitamura, Y., Sendo, T and Asanuma, M.: Serotonin-1A agonist 8-OH-DPAT alleviates motor dysfunction and motor neuron degeneration in a model of amyotrophic lateral sclerosis. Ann. Pharmacol. Pharmaceut., 1(1): 1003, 2016. Murakami, S., Miyazaki, I. and Asanuma, M.: Neuroprotective effect of fermented papaya preparation by activation of Nrf2 pathway in astrocytes. Nutr. Neurosci., published online 14 Nov. 2016. Asanuma, M. and Miyazaki, I.: 3-O-methyldopa inhibits astrocyte-mediated dopaminergic neuroprotective effects of L-DOPA. BMC Neurosci. 17: 52, 2016. doi: 10.1186/s12868-016-0289-0 Takeshima, M., Miyazaki, I., Murakami, S., Kita, T. and Asanuma, M.: L-Theanine protects against excess dopamine-induced neurotoxicity in the presence of astrocytes., J. Clin. Biochem. Nutr., in press. Miyazaki, I. and Asanuma, M.: Serotonin 1A receptors on astrocytes as a potential target for treatment of Parkinson’s disease. Curr. Med. Chem., 23: 676-700, 2016. DOI10.2174/0929867323666160122115057. Miyazaki, I., Murakami, S., Torigoe, N., Kitamura, Y. and Asanuma, M.: Neuroprotective effects of levetiracetam target xCT in astrocytes in parkinsonian mice. J. Neurochem., 136: 194-204, 2016. Murakami, S., Miyazaki, I., Miyoshi, K. and Asanuma, M.: Long-term systemic exposure to rotenone induces central and peripheral pathology of Parkinson’s disease in mice. Neurochem. Res., 40: 1165-1178, 2015. DOI10.1007/s11064-015-1577-2. 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. and 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. 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., 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. and Miyoshi, K.: Cyclooxygenase-independent neuroprotective effects of aspirin 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. 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. 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. and 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. 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. Masato ASANUMA, M.D., Ph.D.