Search for Parkinson-related genes and their functional analysis

2009 Fiscal Year Final Research Report

• Project/Area Number: 17019044
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Osaka University
• Principal Investigator: TODA Tatsushi Osaka University, 大学院・医学研究科, 教授 (30262025)
• Co-Investigator(Kenkyū-buntansha): MURATA Miho 国立精神・神経医療研究センター, 神経内科, 部長 (30282643) ; HATTORI Nobutaka 順天堂大学, 医学部, 教授 (80218510)
• Project Period (FY): 2005 – 2009
• Keywords: パーキンソン病 / 多因子病 / SNP / 病患感受性遺伝子 / 薬剤副作用 / オーダーメイド医療 / マイクロサテライト

Research Abstract

To identify PD-susceptibility variants, we performed a GWAS and two replication studies. Our data show two novel PD-susceptibility loci, involvement of causal genes of autosomal dominant parkinsonism in typical PD, and the possibility that population differences underlie genetic heterogeneity in PD.

Research Products

• [Journal Article] Genome-wide association study identifies common variants at four loci as genetic risk factors for Parkinson's disease (2009)
  • Author(s): Satake W, Nakabayashi Y, Mizuta I, Hirota Y, Ito C, Kubo M, Kawaguchi T, Tsunoda T, Watanabe M, Takeda A, Tomiyama H, Nakashima K, Hasegawa K, Obata F, Yoshikawa T, Kawakami H, Sakoda S, Yamamoto M, Hattori N, Murata M, Nakamura Y, Toda T.
  • Journal Title: Nature Genet 41 Pages: 1303-1307
  • Peer Reviewed
• [Journal Article] Multicenter analysis of glucocerebrosidase mutations in Parkinson's disease (2009)
  • Author(s): Sidransky E, Nalls MA, Aasly JO, Aharon-Peretz J, Annesi G, Barbosa ER, Bar-Shira A, Berg D, Bras J, Brice A, Chen CM, Clark LN, Condroyer C, De Marco EV, Durr A, Eblan MJ, Fahn S, Farrer MJ, Fung HC, Gan-Or Z, Gasser T, Gershoni-Baruch R, Giladi N, Griffith A, Gurevich T, Januario C, Kropp P, Lang AE, Lee-Chen GJ, Lesage S, Marder K, Mata IF, Mirelman A, Mitsui J, Mizuta I, Nicoletti G, Oliveira C, Ottman R, Orr-Urtreger A, Pereira LV, Quattrone A, Rogaeva E, Rolfs A, Rosenbaum H, Rozenberg R, Samii A, Samaddar T, Schulte C, Sharma M, Singleton A, Spitz M, Tan EK, Tayebi N, Toda T, Troiano AR, Tsuji S, Wittstock M, Wolfsberg TG, Wu YR,
  • Journal Title: N Engl J Med 361 Pages: 1651-1661
  • Peer Reviewed
• [Journal Article] Surface plasmon resonance characterization of specific binding of polyglutamine aggregate inhibitors to the expanded polyglutamine stretch. (2009)
  • Author(s): Okamoto Y, Nagai Y, Fujikake N, Popiel HA, Yoshioka T, Toda T, Inui T.
  • Journal Title: Biochem Biophys Res Commun 378 Pages: 634-639
  • Peer Reviewed
• [Journal Article] Delivery of the aggregate inhibitor peptide QBP1 into the mouse brain using PTDs and its therapeutic effect on polyglutamine disease mice. (2009)
  • Author(s): Popiel HA, Nagai Y, Fujikake N, Toda T.
  • Journal Title: Neurosci Lett 449 Pages: 87-92
  • Peer Reviewed
• [Journal Article] Mutations for Gaucher disease confer a high susceptibility to Parkinson disease. (2009)
  • Author(s): Mitsui J, Mizuta I, Toyoda A, Ashida R, Takahashi Y, Goto J, Fukuda Y, Date H, Iwata A, Yamamoto M, Hattori N, Murata M, Toda T, Tsuji S.
  • Journal Title: Arch Neurol 66 Pages: 571-576
  • Peer Reviewed
• [Journal Article] Is g an entity? A Japanese twin study using syllogisms and intelligence tests. (2009)
  • Author(s): Shikishima C, Hiraishi K, Yamagata S, Sugimoto Y, Takemura R, Ozaki K, Okada M, Toda T, Ando J.
  • Journal Title: Intelligence 37 Pages: 256-267
  • Peer Reviewed
• [Journal Article] Residual laminin-binding activity and enhanced dystroglycan glycosylation in novel model mice to dystroglycanopathy. (2009)
  • Author(s): Kanagawa M, Nishimoto A, Chiyonobu T, Takeda S, Miyagoe-Suzuki Y, Wang F, Fujikake N, Taniguchi M, Lu Z, Tachikawa M, Nagai Y, Tashiro F, Miyazaki J, Tajima Y, Takeda S, Endo T, Kobayashi K, Campbell KP, Toda T.
  • Journal Title: Hum Mol Genet 18 Pages: 621-631
  • Peer Reviewed
• [Journal Article] LRRK2 P755L variant in sporadic Parkinson's disease. (2008)
  • Author(s): Tomiyama H, Mizuta I, Li Y, Funayama M, Yoshino H, Li L, Murata M, Yamamoto M, Kubo SI, Mizuno Y, Toda T, Hattori N.
  • Journal Title: J Hum Genet 53 Pages: 1012-1015
  • Peer Reviewed
• [Journal Article] Reduced expression of sarcospan in muscles of Fukuyama congenital muscular dystrophy. (2008)
  • Author(s): Wakayama Y, Inoue M, Kojima H, Yamashita S, Shibuya S, Jimi T, Hara H, Matsuzaki Y, Oniki H, Kanagawa M, Kobayashi K, Toda T.
  • Journal Title: Histol Histopathol 23 Pages: 1425-1438
  • Peer Reviewed
• [Journal Article] Heat shock transcription factor 1 (HSF1)-activating compounds suppress polyglutamine-induced neurodegeneration through induction of multiple molecular chaperones. (2008)
  • Author(s): Fujikake N, Nagai Y, Popiel HA, Okamoto Y, Yamaguchi M, Toda T.
  • Journal Title: J Biol Chem 283 Pages: 26188-26197
  • Peer Reviewed
• [Journal Article] Pikachurin, a dystroglycan ligand, is essential for photoreceptor ribbon synapse formation (2008)
  • Author(s): Sato S, Omori Y, Katoh K, Kondo M, Kanagawa M, Miyata K, Funabiki K, Koyasu T, Kajimura N, Miyoshi T, Sawai H, Kobayashi K Tani A, Toda T, Usukura J, Tano Y, Fujikado T, Furukawa T.
  • Journal Title: Nature Neurosci 11 Pages: 923-931
  • Peer Reviewed
• [Journal Article] Calbindin 1, fibroblast growth factor 20, and・-synuclein in Parkinson's disease. (2008)
  • Author(s): Mizuta I, Tsunoda T, Satake W, Nakabayashi Y, Watanabe M, Takeda A, Hasegawa K, Nakashima K, Yamamoto M, Hattori N, Murata M, Toda T.
  • Journal Title: Hum Genet 124 Pages: 89-94
  • Peer Reviewed
• [Journal Article] Mutation analysis of the PINK1 gene in 391 patients with Parkinson's disease (2008)
  • Author(s): Kumazawa R, Tomiyama H, Li Y, Imamichi Y, Funayama M, Yoshino H, Yokochi F, Fukusako T, Takehisa Y, Kashihara K, Kondo T, Elibol B, Bostantjopoulou S, Toda T, Takahashi H, Yoshii F, Mizuno Y, Hattori N.
  • Journal Title: Arch Neurol 65 Pages: 802-808
  • Peer Reviewed
• [Journal Article] Seizure-genotype relationship in Fukuyama-type congenital muscular dystrophy. (2008)
  • Author(s): Yoshioka M, Higuchi Y, Fujii T, Aiba H, Toda T.
  • Journal Title: Brain Dev 30 Pages: 59-67
  • Peer Reviewed
• [Journal Article] Genetically regulated epigenetic transcriptional activation of retrotransposon insertion confers mouse dactylaplasia phenotype. (2007)
  • Author(s): Kano H, Kurahashi H, Toda T.
  • Journal Title: Proc Natl Acad Sci USA 104 Pages: 19034-19039
  • Peer Reviewed
• [Journal Article] Detection of polyglutamine protein oligomers in cells by fluorescence correlation spectroscopy. (2007)
  • Author(s): Takahashi Y, Okamoto Y, Popiel HA, Fujikake N, Toda T, Kinjo M, Nagai Y.
  • Journal Title: J Biol Chem 282 Pages: 24039-24048
  • Peer Reviewed
• [Journal Article] Redefining the disease locus of 16q22. 1-linked autosomal dominant cerebellar ataxia. (2007)
  • Author(s): Amino T, Ishikawa K, Toru S, Ishiguro T, Sato N, Tsunemi T, Murata M, Kobayashi K, Inazawa J, Toda T, Mizusawa H.
  • Journal Title: J Hum Genet 52 Pages: 643-649
  • Peer Reviewed
• [Journal Article] Partial tandem duplication of GRIA3 in a male with mental retardation. (2007)
  • Author(s): Chiyonobu T, Hayashi S, Kobayashi K, Morimoto M, Miyanomae Y, Nishimura A, Nishimoto A, Ito C, Imoto I, Sugimoto T, Jia Z, Inazawa J, Toda T.
  • Journal Title: Am J Med Genet 143 Pages: 1448-1455
  • Peer Reviewed
• [Journal Article] Fibroblast growth factor 20 gene and Parkinson's disease in the Japanese population (2007)
  • Author(s): Satake W, Mizuta I, Suzuki S, Nakabayashi Y, Ito C, Watanabe M, Takeda A, Hasegawa K, Sakoda S, Yamamoto M, Hattori N, Murata M, Toda T.
  • Journal Title: Neuroreport 18 Pages: 937-940
  • Peer Reviewed
• [Journal Article] A toxic monomeric conformer of the polyglutamine protein. (2007)
  • Author(s): Nagai Y, Inui T, Popiel HA, Fujikake N, Hasegawa K, Urade Y, Goto Y, Naiki H, Toda T.
  • Journal Title: Nature Struct Mol Biol 14 Pages: 332-340
  • Peer Reviewed
• [Journal Article] Defective peripheral nerve myelination and neuromuscular junction formation in fukutin-deficient chimeric mouse. (2007)
  • Author(s): Saito F, Masaki T, Saito Y, Nakamura A, Takeda S, Shimizu T, Toda T, Matsumura K.
  • Journal Title: J Neurochem 101 Pages: 1712-1722
  • Peer Reviewed
• [Journal Article] LRRK2 G2385R variant is a risk factor for parkinson disease in Asian population. (2007)
  • Author(s): Funayama M, Li Y, Tomiyama H, Yoshino H, Imamichi Y, Yamamoto M, Murata M, Toda T, Mizuno Y, Hattori N.
  • Journal Title: Neuroreport 18 Pages: 273-275
  • Peer Reviewed
• [Journal Article] Protein transduction domain-mediated delivery of QBP1 suppresses polyglutamine- induced neurodegeneration in vivo. (2007)
  • Author(s): Popiel HA, Nagai Y, Fujikake N, Toda T.
  • Journal Title: Mol Ther 15 Pages: 303-309
  • Peer Reviewed
• [Journal Article] Registry of adolescent and young adult twins in the Tokyo area. (2006)
  • Author(s): Shikishima C, Ando J, Ono Y, Toda T, Yoshimura K.
  • Journal Title: Twin Res Hum Genet 9 Pages: 811-816
  • Peer Reviewed
• [Journal Article] The genetic and molecular basis of muscular dystrophy: roles of cell-matrix linkage in the pathogenesis. (2006)
  • Author(s): Kanagawa M, Toda T.
  • Journal Title: J Hum Genet 51 Pages: 915-927
  • Peer Reviewed
• [Journal Article] Molecular interaction between fukutin and POMGnT1 in the glycosylation pathway of a-dystroglycan. (2006)
  • Author(s): Xiong H, Kobayashi K, Tachikawa M, Manya H, Takeda S, Chiyonobu T, Fujikake N, Wang F, Nishimoto A, Morris GE, Nagai Y, Kanagawa M, Endo T, Toda T.
  • Journal Title: Biochem Biophys Res Commun 350 Pages: 935-941
  • Peer Reviewed
• [Journal Article] Candidate genes for male factor infertility- validation. (2006)
  • Author(s): Mori T, Kurahashi H, Shinka T, Nakahori Y, Taniguchi M, Toda T, Iwamoto T.
  • Journal Title: Fertil Steril 86 Pages: 1553-1554
  • Peer Reviewed
• [Journal Article] A case of Fukuyama-type congenital muscular dystrophy with a very mild mental deficit. (2006)
  • Author(s): Hino-Fukuyo N, Haginoya K, Hayashi YK, Nishino I, Murakami T, Nonaka I, Togashi K, Tanaka S, Takayanagi M, Yokoyama H, Sakamoto O, Abe T, Toda T, Iinuma K.
  • Journal Title: Neuromuscul Disord 16 Pages: 274-276
  • Peer Reviewed
• [Journal Article] Aberrant neuromuscular junctions and delayed terminal muscle fiber maturation in・-dystroglycanopathies (2006)
  • Author(s): Taniguchi M, Kurahashi H, Noguchi S, Fukudome T, Okinaga T, Tsukahara T, Tajima Y, Ozono K, Nishino I, Nonaka I, Toda T.
  • Journal Title: Hum Mol Genet 15 Pages: 1279-1289
  • Peer Reviewed
• [Journal Article] Multiple candidate gene analysis identifies a-synuclein as a susceptibility gene for sporadic Parkinson's disease. (2006)
  • Author(s): Mizuta I, Satake W, Nakabayashi Y, Ito C, Suzuki S, Momose Y, Nagai Y, Oka A, Inoko H, Fukae J, Saito Y, Sawabe M, Murayama S, Yamamoto M, Hattori N, Murata M, Toda T.
  • Journal Title: Hum Mol Genet 15 Pages: 1151-1158
  • Peer Reviewed
• [Journal Article] Expression profiling of muscles from Fukuyama-type congenital muscular dystrophy and laminin-・2 deficient congenital muscular dystrophy; is congenital muscular dystrophy a primary fibrotic disease? (2006)
  • Author(s): Taniguchi M, Kurahashi H, Noguchi S, Sese J, Okinaga T, Tsukahara T, Guicheney P, Ozono K, Nishino I, Morishita S, Toda T.
  • Journal Title: Biochem Biophys Res Commun 342 Pages: 489-502
  • Peer Reviewed
• [Journal Article] Clinical heterogeneity of a-synuclein gene duplication in Parkinson's disease. (2006)
  • Author(s): Nishioka K, Hayashi S, Farrer MJ, Singleton AB, Yoshino H, Imai H, Kitami T, Sato K, Kuroda R, Tomiyama H, Mizoguchi K, Murata M, Toda T, Imoto I, Inazawa J, Mizuno Y, Hattori N.
  • Journal Title: Ann Neurol 59 Pages: 298-309
  • Peer Reviewed
• [Journal Article] Clinicogenetic study of mutations in LRRK2 exon 41 in Parkinson's disease patients from 18 countries. (2006)
  • Author(s): Tomiyama H, Li Y, Funayama M, Hasegawa K, Yoshino H, Kubo S, Sato K, Hattori T, Lu CS, Inzelberg R, Djaldetti R, Melamed E, Amouri R, Gouider-Khouja N, Hentati F, Hatano Y, Wang M, Imamichi Y, Mizoguchi K, Miyajima H, Obata F, Toda T, Farrer MJ, Mizuno Y, Hattori N.
  • Journal Title: Mov Disord 21 Pages: 1102-1108
  • Peer Reviewed
• [Journal Article] Cytoprotective effect of novel histone deacetylase inhibitors against polyglutamine toxicity. (2006)
  • Author(s): Kariya S, Hirano M, Uesato S, Nagai Y, Nagaoka Y, Furiya Y, Asai H, Fujikake N, Toda T, Ueno S.
  • Journal Title: Neurosci Lett 392 Pages: 213-215
  • Peer Reviewed
• [Journal Article] Clinicogenetic study of PINK1 mutations in autosomal recessive early-onset parkinsonism (2005)
  • Author(s): Li Y, Tomiyama H, Sato K, Hatano Y, Yoshino H, Atsumi M, Kitaguchi M, Sasaki S, Kawaguchi S, Miyajima H, Toda T, Mizuno Y, Hattori N.
  • Journal Title: Neurology 64 Pages: 1955-1957
  • Peer Reviewed
• [Journal Article] Humanin attenuates apoptosis induced by DRPLA proteins with expanded polyglutamine stretches. (2005)
  • Author(s): Kariya S, Hirano M, Nagai Y, Furiya Y, Fujikake N, Toda T, Ueno S.
  • Journal Title: J Mol Neurosci 25 Pages: 165-169
  • Peer Reviewed
• [Journal Article] Basement membrane fragility underlies embryonic lethality in fukutin-null mice. (2005)
  • Author(s): Kurahashi H, Taniguchi M, Meno C, Taniguchi Y, Takeda S, Horie M, Otani H, Toda T.
  • Journal Title: Neurobiol Dis 19 Pages: 208-217
  • Peer Reviewed
• [Journal Article] Effects of fukutin deficiency in the developing mouse brain. (2005)
  • Author(s): Chiyonobu T, Sasaki J, Nagai Y, Takeda S, Funakoshi H, Nakamura T, Sugimoto T, Toda T.
  • Journal Title: Neuromuscul Disord 15 Pages: 416-426
  • Peer Reviewed
• [Journal Article] b4GalT-II is a key regulator of glycosylation of the proteins involved in neuronal development. (2005)
  • Author(s): Sasaki N, Manya H, Okubo R, Kobayashi K, Ishida H, Toda T, Endo T, Nishihara S.
  • Journal Title: Biochem Biophys Res Commun 333 Pages: 131-137
  • Peer Reviewed
• [Journal Article] Alternative splicing regulates the transcriptional activity of Drosophila heat shock transcription factor in response to heat/cold stress. (2005)
  • Author(s): Fujikake N, Nagai Y, Popiel HA, Kano H, Yamaguchi M, Toda T.
  • Journal Title: FEBS lett 579 Pages: 3842-3848
  • Peer Reviewed
• [Journal Article] An autosomal dominant cerebellar ataxia linked to chomosome 16q22.1 is associated with a single-nucleotide substitution in the 5ォ untranslated region of the gene encoding a novel protein with spectrin repeat and rho Guanine-nucleotide exchange-factor domains. (2005)
  • Author(s): Ishikawa K, Toru S, Tsunemi T, Li M, Kobayashi K, Yokota T, Amino T, Owada K, Fujigasaki H, Sakamoto M, Tomimitsu H, Takashima M, Kumagai J, Noguchi Y, Kawashima Y, Ohkoshi N, Ishida G, Gomyoda M, Yoshida M, Hashizume Y, Saito Y, Murayama S, Yamanouchi H, Mizutani T, Kondo I, Toda T, Mizusawa H.
  • Journal Title: Am J Hum Genet 77 Pages: 280-296
  • Peer Reviewed
• [Journal Article] Founder SVA retrotransposal insertion in Fukuyama-type congenital muscular dystrophy and its origin in Japanese and Northeast Asian populations. (2005)
  • Author(s): Watanabe M, Kobayashi K, Jin F, Park KS, Yamada T, Tokunaga K, Toda T.
  • Journal Title: Am J Med Genet 138 Pages: 344-348
  • Peer Reviewed
• [Journal Article] Genomic rearrangement at 10q24 in non-syndromic split-hand/split-foot malformation. (2005)
  • Author(s): Kano H, Kurosawa K, Horii E, Ikegawa S, Yoshikawa H, Kurahashi H, Toda T.
  • Journal Title: Hum Genet 118 Pages: 477-483
  • Peer Reviewed
• [Journal Article] Unique tauopathy in Fukuyama-type congenital muscular dystrophy. (2005)
  • Author(s): Saito Y, Motoyoshi Y, Kashima K, Izumiyama-Shimomura N, Toda T, Nakano I, Hasegawa M, Murayama S.
  • Journal Title: J Neuropath Exp Neurol 64 Pages: 1118-1126
  • Peer Reviewed
• [Journal Article] Fukutin and a-dystroglycanopahties (2005)
  • Author(s): Toda T, Chiyonobu T, Xiong H, Tachikawa M, Kobayashi K, Manya H, Takeda S, Taniguchi M, Kurahashi H, EndoT.
  • Journal Title: Acta Myologica 24 Pages: 60-63
  • Peer Reviewed
• [Remarks] ホームページ
  • URL: http://www.med.kobe-u.ac.jp/im3/rinsyo/shinkei/index.html
• [Remarks]
  • URL: http://www.med.kobe-u.ac.jp/clgene/
• [Remarks] 新聞発表、その他顕著なもの
• [Remarks] GWASによるパーキンソン病関連遺伝子同定平成21年11月16日、24日、NHKニュース、日本経済新聞、朝日新聞、毎日新聞、産経新聞、東京新聞、など