国立精神・神経医療研究センター神経研究所疾病研究第四部- Index

Publications -研究業績

2022年度

刊行物

Kishino Y, Matsukawa K, Matsumoto T, Miyazaki R, Wakabayashi T, Nonaka T, Kametani F, Hasegawa M, Hashimoto T, Iwatsubo T: Casein kinase 1δ/ε phosphorylates fused in sarcoma (FUS) and ameliorates FUS-mediated neurodegeneration. J Biol Chem 298(8): 102191, Jun, 2022

学会発表

特別講演・シンポジウム

橋本唯史：アミロイド蓄積を誘発するAβオリゴマーとアルツハイマー病脳老人斑の進展. 第63回日本神経病理学会総会シンポジウム, 京都, 2022/06/26

一般学会

Uchigami H, Kashiwagi-Hakozaki M, Matsubara T, Murayama S, Saito Y, Toda T, Hashimoto T, Iwatsubo T: Soluble high-molecular-weight Ab species inducing cerebral b-amylodosis are abundant in Alzheimer brains with prominent cerebral amyloid angiopathy.Neuro2022 ポスター, 沖縄, 2022/06/30
箱崎眞結, 牛久哲男, 橋本唯史, 岩坪威: アルツハイマー病患者脳由来Abオリゴマーのin vivoにおけるAb蓄積誘発効果の検討. 第111回日本病理学会総会ポスター, 神戸, 2022/4/14

2021年度

刊行物

Ishida K, Yamada K, Nishiyama R, Hashimoto T, Nishida I, Abe Y, Yasui M, Iwatsubo T: Glymphatic system clears extracellular tau and protects from tau aggregation and neurodegeneration. J Exp Med　219(3): e20211275, Mar, 2022
Kaneshiro N, Komai M, Imaoka R, Ikeda A, Kamikubo Y, Saito T, Saido TC, Tomita T, Hashimoto T, Iwatsubo T, Sakurai T, Uehara T, Takasugi N: Lipid flippase dysfunction as a therapeutic target for endosomal anomalies in Alzheimer’s disease. iScience 25(3): 103869, Mar, 2022
An H, Litscher G, Watanabe N, Wei W, Hashimoto T, Iwatsubo T, Buchman VL, Shelkovnikova TA: ALS-linked cytoplasmic FUS assemblies are compositionally different from physiological stress granules and sequester hnRNPA3, a novel modifier of FUS toxicity: Neurobiol Dis, 162: 105585, Jan, 2022
Matsukawa K, Kukharsky MS, Park SK, Park S, Watanabe N, Iwatsubo T, Hashimoto T, Liebman SW, Shelkovnikova TA: Long non-coding RNA NEAT1_1 ameliorates TDP-43 toxicity in in vivo models of TDP-43 proteinopathy. RNA Biol, 18(11): 1546-1554, Nov, 2021

学会発表

特別講演・シンポジウム

橋本唯史：FUSの多量体化と神経毒生・伝播. 第40回日本認知症学会学術集会シンポジウム, 東京, 2021/11/27
橋本唯史：Abエコノミーとアルツハイマー病. 生物化学的測定研究会第26回学術集会シンポジウム, オンライン, 2021/6/4

国際学会

Hashimoto T, Kokawa A, Tanaka M, Ohno Y, Kashiwagi-Hakozaki M, Iwatsubo T: Isoform- and dose-dependent effects of apolipoprotein E in the deposition of Ab in the brain of APP transgenic mice．Neuroscience2021, Poster P216, Online 2021/11/11
Kashiwagi-Hakozaki M, Naka Y, Dooley P, Frosch MP, Hyman BT, Fukayama M, Ushiku T, Hashimoto T, Iwatsubo T: Soluble high-molecular-weight Ab oligomers derived from the Ab-laden brains induce cerebral b-amyloidosis. ADPD2021, Poster, Barcelona (online) 2021/3/9

一般学会

箱崎眞結, 牛久哲男, 橋本唯史, 岩坪威: アルツハイマー病患者脳由来Ab seed分子のin vivoにおけるAb蓄積誘発効果の検討. 第40回日本認知症学会学術集会ポスター, 東京, 2021/11/26
宮崎良太, 松川浩二, 橋本唯史, 岩坪威: ULK1がTDP-43の生理学的及び病的機能に与える役割の検討. 第40回日本認知症学会学術集会ポスター, 東京, 2021/11/26
田中麻衣子, 粉川明日香, 橋本唯史, 岩坪威: ヒトapoEがAbの蓄積過程に与える影響の検討. 第40回日本認知症学会学術集会ポスター, 東京, 2021/11/26

その他

橋本唯史: アルツハイマー病基礎研究の最前線. 東京農工大―国立精神・神経医療研究センター第6回合同シンポジウム, オンライン, 2022/02/15

2020年度以前

原著

Hashimoto T, Fujii D, Naka Y, Kashiwagi-Hakozaki M, Matsuo Y, Matsuura Y, Wakabayashi T, Iwatsubo T: Collagenous Alzheimer amyloid plaque component impacts on the compaction of amyloid-b plaques. Acta Neuropathol Commun 8(1), 212, 2020
Abe Y, Ikegawa N, Yoshida K, Muramatsu K, Hattori S, Kawai K, Murakami M, Tanaka T, Goda W, Goto M, Yamamoto T, Hashimoto T, Yamada K, Shibata T, Misawa H, Mimura M, Tanaka KF, Miyakawa T, Iwatsubo T, Hata J, Niikura T, Yasui M: Behavioral and electrophysiological evidence for a neuroprotective role of aquaporin-4 in the 5xFAD transgenic mice model. Acta Neuropathol Commun 8(1), 67, 2020
Munezane H, Oizumi H, Wakabayashi T, Nishio S, Hirasawa T, Sato T, Harada A, Yoshida T, Eguchi T, Yamanashi Y, Hashimoto T, Iwatsubo T: Roles of collagen XXV and its putative receptors PTP d/s in intramuscular motor innervation and congenital cranial dysinnervation disorder. Cell Rep 29(13), 4362-4376, 2019
Park S, Park SK, Watanabe N, Hashimoto T, Iwatsubo T, Shelkovnikova TA, Liebman SW: Calcium-responsive transactivator (CREST) toxicity is rescued by loss of PBP1/ATXN2 function in a novel yeast proteinopathy model and in transgenic flies. PLoS Genet 15(8), e1008308, 2019
Eto M, Hashimoto T, Shimizu T, Iwatsubo T: Characterization of the unique in vitro effects of unsaturated fatty acids on the formation of amyloid b fibrils. PLoS ONE 14(7), e0219465, 2019
Wakabayashi T, Yamaguchi K, Matsui K, Sano T, Kubota T, Hashimoto T, Mano A, Yamada K, Matsuo Y, Kubota N, Kadowaki T, Iwatsubo T: Differential effects of diet- and genetically-induced brain insulin resistance on amyloid pathology in a mouse model of Alzheimer’s disease. Mol Neurodegener 14(1), 15, 2019
Bannai T, Mano T, Chen X, Ohtomo G, Ohtomo R, Tsuchida T, Koshi-Mano K, Hashimoto T, Okazawa H, Iwatsubo T, Tsuji S, Toda T, Iwata A: Chronic cerebral hypoperfusion shifts the equilibrium of amyloid β oligomers to aggregation-prone species with higher molecular weight. Scientific Rep 9(1), 2827, 2019
Mann DMA, Davidson YS, Robinson AC, Allen N, Hashimoto T, Richardson A, Jones M, Snowden JS, Pendleton N, Potter MC, Laquerrière A, Prasher V, Iwatsubo T, Strydom A: Patterns and severity of vascular amyloid in Alzheimer’s disease associated with duplication and missense mutations in APP gene, Down Syndrome and sporadic Alzheimer’s disease. Acta Neuropathol 136(4), 569-587, 2018
Matsumoto T, Matsukawa K, Watanabe N, Kishino Y, Kunugi H, Ihara R, Wakabayashi T, Hashimoto T, Iwatsubo T: Self-assembly of FUS through its low-complexity domain contributes to neurodegeneration. Hum Mol Genet 27(8), 1353-1365, 2018
Mano T, Nagata K, Nonaka T, Tarutani A, Imamura T, Hashimoto T, Bannai T, Koshi-Mano K, Tsuchida T, Ohtomo R, Takahashi-Fujigasaki J, Yamashita S, Ohyagi Y, Yamazaki R, Tsuji S, Tamaoka A, Ikeuchi T, Saido TC, Iwatsubo T, Ushizima T, Murayama S, Hasegawa M, Iwata A: Neuron-specific methylome analysis reveals epigenetic regulation and tau-related dysfunction of BRCA1 in Alzheimer’s disease. Proc Natl Acad Sci USA 114(45), E9645-E9654, 2017
Arbel-Ornath M, Hudry E, Bovine JR, Hashimoto T, Takeda S, Kuchbhotla KV, Hou S, Lattarulo CR, Belcher AM, Shakerdge N, Trujillo PB, Muzikansky A, Betensky RA,Hyman BT, Bacskai BJ: Soluble oligomeric amyloid-b induces calcium dyshomeostasis that precedes synapse loss in the living mouse brain. Mol Neurodegener 12(1), 27, 2017
Matsukawa K, Hashimoto T, Matsumoto T, Ihara R, Chihara T, Miura M, Wakabayashi T, Iwatsubo T: Familial ALS-linked mutations in Profilin 1 exacerbated TDP-43 induced degeneration in the retina of Drosophila Melanogaster through an increase in the cytoplasmic localization of TDP-43. J Biol Chem 291(45), 23464-23476, 2016
Hori Y, Hashimoto T, Nomoto H, Hyman BT, Iwatsubo T: Role of apolipoprotein E in b-amyloidgenesis: isoform-specific effects on protofibril to fibril conversion of Ab in vitro and brain Ab deposition in vivo. J Biol Chem 290(24), 15163-15174, 2015
Yamamoto K, Tanei Z, Hashimoto T, Wakabayashi T, Okuno H, Naka Y, Yizhar O, Fenno LE, Fukayama M, Bito H, Cirrito JR, Holtzman DM, Deisseroth K, Iwatsubo T: Chronic optogenetic activation augments Ab pathology in a mouse model of Alzheimer disease. Cell Rep 11(6), 859-865, 2015
Kukharsky MS, Quintiero A, Matsumoto T, Matsukawa K, An H, Hashimoto T, Iwatsubo T, Buchman VL, Shelkovnikova TA: Calcium-responsive transactivator (CREST) protein shares a set of structural and functional traits with other proteins associated with amyotrophic lateral sclerosis. Mol. Neurodegener. 10, 20, 2015
Tanaka T, Wakabayashi T, Oizumi H, Nishio S, Sato T, Harada A, Fujii D, Matsuo Y, Hashimoto T, Iwatsubo T: CLAC-P/Collagen type XXV is required for the intramuscular innervation of motoneurons during neuromuscular development. J Neurosci 34(4), 1370-1379, 2014
Farrar CT, William CM, Hudry E, Hashimoto T, Hyman BT: RNA aptamer probes as optical imaging agents for the detection of amyloid plaques. PLoS One 9(2), e89901, 2014
Hudry E, Dashkoff J, Roe AD, Takeda S, Koffie RM, Hashimoto T, Scheel M, Spires-Jones T, Arbel-Ornath M, Betensky R, Davidson BL, Hyman BT: Gene transfer of human Apoe Isoforms results in differential modulation of amyloid deposition and neurotoxicity in mouse brain. Sci Trans Med 5 (212), 212ra161, 2013
Ihara R, Matsukawa K, Nagata Y, Kunugi H, Tsuji S, Chihara T, Kuranaga E, Miura M, Wakabayashi T, Hashimoto T, Iwatsubo T: RNA binding mediates neurotoxicity in the transgenic Drosophila model of TDP-43 proteinopathy. Hum Mol Genet 22(22), 4474-4484, 2013
Cho H, Hashimoto T, Wong E, Hori Y, Wood LB, Zhao L, Haigis KM, Hyman BT, Irimia D: Microfluidic chemotaxis platform for differentiating the roles of soluble and bound amyloid-b on microglia accumulation. Sci. Rep. 3, 1823, 2013
Takeda S, Hashimoto T, Serrano-Pozo A, Roe AD, Spires-Jones TL, Hyman BT: Brain interstitial oligomeric amyloid b increases with age and is resistant to clearance from brain in a mouse model of Alzheimer’s disease. FASEB J 27(8), 3239-3248, 2013
Li X, Uemura K, Hashimoto T, Nasser-Ghodsi N, Arimon M, Lill CM, Palazzolo I, Krainc D, Hyman BT, Berezovska O: Neuronal activity and secreted amyloid b lead to altered amyloid b precursor protein and presenilin 1 interactions. Neurobiol Dis 50, 127-134, 2013
Hashimoto T, Serrano-Pozo A, Hori Y, Adams KW, Takeda S, Banerji AO, Mitani A, Joyner D, Thyssen DH, Bacskai BJ, Frosch MP, Spires-Jones TL, Finn MB, Holtzman DM, Hyman BT: Apolipoprotein E, especially apolipoprotein E4, increases the oligomerization of amyloid b peptide. J Neurosci 32(43), 15181-15192, 2012
Tai HC, Serrano-Pozo A, Hashimoto T, Frosch MP, Spires-Jones TL, Hyman BT: The synaptic accumulation of hyperphosphorylated tau oligomers in Alzheimer disease is associated with dysfunction of the ubiquitin-proteasome system. Am J Pathol 181(4), 1426-1435, 2012
Koffie RM, Hashimoto T, Tai HC, Kay KR, Serrano-Pozo A, Joyner D, Hou S, Kopeikina KJ, Frosch MP, Lee VM, Holtzman DM, Hyman BT, Spires-Jones TL: Apolipoprotein E4 effects in Alzheimer disease are mediated by synaptotoxic oligomeric amyloid-b. Brain 135(7), 2155-2168, 2012
Wu HY, Hudry E, Hashimoto T, Uemura K, Fan ZY, Berezovska O, Grosskreutz CL, Bacskai BJ, Hyman BT: Distinct dendritic spine and nuclear phases of Calcineurin activation after exposure to amyloid-b revealed by a novel fluorescence resonance energy transfer assay. J Neurosci 32(15), 5298-5309, 2012
Ofengeim D, Shi P, Miao B, Fan J, Xia X, Fan Y, Lipinski MM, Hashimoto T, Polydoro M, Yuan J, Wong STC, Degterev A: Identification of small molecule inhibitors of neurite loss induced by Ab peptide using high-content screening. J Biol Chem 287(12), 8714-8723, 2012
Hudry E, Wu HY, Arbel-Ornath M, Hashimoto T, Matsouaka R, Fan Z, Spires-Jones T, Betensky R, Bacskai BJ, Hyman BT: Inhibition of the NFAT pathway alleviates amyloid b neurotoxicity in a mouse model of Alzheimer’s disease. J Neurosci 32(9), 3176-3192, 2012
DaRocha-Souto B, Coma M, Perez-Nievas BG, Scotton TC, Siao M, Sanchez-Ferrer P, Hashimoto T, Fan Z, Hudry E, Barroeta I, Serenó L, Rodríguez M, Sánchez MB, Hyman BT, Gómez-Isla T: Activation of glycogen synthase kinase-3 b mediates b-amyloid induced neuritic damage in Alzheimer’s disease. Neurobiol Dis 45(1), 425-437, 2012
Hashimoto T, Adams KW, Fan Z, McLean PJ, Hyman BT: Characterization of the oligomer formation of amyloid b peptide using a split-luciferase complementation assay. J Biol Chem 286(31), 27081-27091, 2011
Fujiyoshi M, Tachikawa M, Ohtsuki S, Ito S, Uchida Y, Akanuma S, Kamiie J, Hashimoto T, Hosoya K, Iwatsubo T, Terasaki T: Amyloid-b peptide (1-40) elimination from cerebrospinal fluid involves low-density lipoprotein receptor-related protein 1 at the blood-cerebrospinal fluid barrier. J Neurochem 118(3), 407-415, 2011
DaRocha-Souto B, Scotton TC, Coma M, Serrano-Pozo A, Hashimoto T, Serenó L, Rodríguez M, Sánchez B, Hyman BT, Gómez-Isla T: Brain oligomeric b–amyloid but not total amyloid plaque burden correlates with neuronal loss and astrocyte inflammatory response in amyloid precursor protein/tau transgenic mice. J Neuropathol Exp Neurol 70(5), 360-376, 2011
Jones PB, Adams KW, Rozkalne A, Spires-Jones TL, Hshieh TT, Hashimoto T, von Armin CAF, Mielke M, Bacskai BJ, Hyman BT: Apolipoprotein E: Isoform specific differences in tertiary structure and interaction with amyloid-b in human Alzheimer brain. PLoS ONE 6(1), e14586, 2011
Danzer KM, Ruf WP, Putcha P, Joyner D, Hashimoto T, Glabe C, Hyman BT, McLean PJ: Heat shock protein 70 modulates toxic extracellular a-synuclein oligomers and rescues trans-synaptic toxicity. FASEB J 25(1), 326-336, 2011
Uemura K, Farner KC, Hashimoto T, Nasser-Ghodsi N, Wolfe M , Koo EH, Hyman BT, Berezovska O: Substrate docking to g-secretase allows access of g-secretase modulators to an allosteric site. Nat Commun 1, 130, 2010
Wu HY, Hudry E, Hashimoto T, Kuchibhotla K, Rozkalne A, Fan X, Spires-Jones T, Xie H, Arbel-Ornath M, Grosskreutz CL, Bacskai BJ, Hyman BT: Amyloid b induces the morphological neurodegenerative triad of spine loss, dendritic simplification, and neuritic dystrophies through calcineurin activation. J Neurosci 30(7), 2636-2649, 2010
Yamada K, Yabuki C, Seubert P, Schenk D, Hori Y, Ohtsuki S, Terasaki T, Hashimoto T, Iwatsubo T: Ab immunotherapy: intracerebral sequestration of Ab by anti-Ab monoclonal antibody 266 with high affinity to soluble Ab. J Neurosci 29(36), 11393-11398, 2009
Koffie RM, Meyer-Luehmann M, Hashimoto T, Adams KW, Mielke ML, Garcia-Alloza M,Micheva KD, Smith SJ, Kim ML, Lee VM, Hyman BT, Spires-Jones TL: Oligomeric amyloid beta associates with postsynaptic densities and correlates with excitatory synapse loss near senile plaques. Proc Natl Acad Sci USA 106(10), 4012-4017, 2009
Yamada K, Hashimoto T, Yabuki C, Nagae Y, Tachikawa M, Strickland DK, Liu Q, Bu G, Basak JM, Holtzman DM, Ohtsuki S, Terasaki T, Iwatsubo T: The low density lipoprotein receptor-related protein 1 mediates uptake of amyloid b peptides in an in vitro model of the blood-brain barrier cells. J Biol Chem 283(50), 34554-34562, 2008
Yoshihara T, Takiguchi S, Kyuno A, Tanaka K, Kuba S, Hashiguchi S, Ito Y, Hashimoto T, Iwatsubo T, Tsuyama S, Nakashima T, Sugimura K: Immunoreactivity of phage library-derived human single-chain antibodies to amyloid beta conformers in vitro. J Biochem 143(4), 475-486, 2008
Akanuma S, Ohtsuki S, Doi Y, Tachikawa M, Ito S, Hori S, Asashima T, Hashimoto T, Yamada K, Ueda K, Iwatsubo T, Terasaki T: ATP binding cassette transporter A1 (ABCA1) deficiency does not attenuate the brain-to-blood efflux transport of human amyloid-b peptide (1-40) at the blood-brain barrier. Neurochem Int 52(6), 956-961, 2008
Kato M, Kinoshita H, Enokita M, Hori Y, Hashimoto T, Iwatsubo T, Toyo’oka T: Analytical method for b-amyloid fibrils using CE-laser induced fluorescence and its application to screening for inhibitors of b-amyloid protein aggregation. Anal Chem 79(13), 4887-4891, 2007
Hori Y, Hashimoto T, Wakutani Y, Urakami K, Nakashima K, Condron MM, Tsubuki S, Saido TC, Teplow DB, Iwatsubo T: The Tottori (D7N) and English (H6R) familial Alzheimer’s disease mutations accelerate Ab fibril formation without increasing protofibril formation. J Biol Chem 282(7), 4916-4923, 2007
Tamaki C, Ohtsuki S, Iwatsubo T, Hashimoto T, Yamada K, Yabuki C, Terasaki T: Major involvement of low-density lipoprotein receptor-related protein 1 in the clearance of plasma free amyloid b-peptide by the liver. Pharma Res 23(7), 1407-1416, 2006
Osada Y, Hashimoto T, Nishimura A, Matsuo Y, Wakabayashi T, Iwatsubo T: CLAC binds to amyloid b peptides through the positively-charged amino acid cluster within the collagen domain 1 and inhibits formation of amyloid fibrils. J Biol Chem 280(9), 8596-8605, 2005
Kowa H, Sakakura T, Matsuura Y, Wakabayashi T, Mann DMA, Duff K, Tsuji S, Hashimoto T, Iwatsubo T: Mostly separate distributions of CLAC- versus Ab40- or thioflavin S-reactivities in senile plaques reveal two distinct subpopulations of b-amyloid deposits. Am J Pathol 165(1), 273-281, 2004
Wakutani Y, Watanabe K, Adachi Y, Wada-Isoe K, Urakami K, Ninomiya H, Saido TC, Hashimoto T, Iwatsubo T, Nakashima K: Novel amyloid precursor protein missense mutation (D678N) in familial Alzheimer’s disease. J Neurol Neurosurg Psychiatr 75(7), 1039-1042, 2004
Söderberg L, Zhukareva V, Bogdanovic N, Hashimoto T, Winblad B, Iwatsubo T, Lee VMY, Trojanowski JQ, Näslund J: Molecular Identification of AMY, an Alzheimer disease amyloid-associated protein. J Neuropathol Exp Neurol 62(11), 1108-1117, 2003
Hashimoto T, Wakabayashi T, Watanabe A, Kowa H, Hosoda R, Nakamura A, Kanazawa I, Arai T, Takio K, Mann DMA, Iwatsubo T: CLAC: a novel Alzheimer amyloid plaque component derived from a transmembrane precursor, CLAC-P/collagen type XXV. EMBO J 21(7), 1524-1534, 2002
Houlden H, Baker M, McGowan E, Lewis P, Hutton M, Crook R, Wood NW, Kumar-Singh S, Geddes J, Swash M, Scaravilli F, Holton JL, Lashley T, Tomita T, Hashimoto T, Verkkoniemi A, Kalimo H, Somer M, Paetau A, Martin JJ, Van Broeckhoven C, Golde T, Hardy J, Haltia M, Revesz T: Variant Alzheimer’s disease with spastic paraparesis and cotton wool plaques is caused by PS-1 mutations that lead to exceptionally high amyloid-b concentrations. Ann Neurol 48(5), 806-808, 2000
Tomita T, Tokuhiro S, Hashimoto T, Aiba K, Saido TC, Maruyama K, Iwatsubo T: Molecular dissection of domains in mutant presenilin 2 that mediate overproduction of amyloidogenic forms of amyloid b peptides: Inability of truncated forms of PS2 with familial Alzheimer’s disease mutation to increase secretion of Ab42. J Biol Chem 273(33), 21153-21160, 1998

国立精神・神経医療研究センター
神経研究所疾病研究第四部

Publications

Department of Degenerative Neurological Diseases

橋本唯史部長

略歴

Publications -研究業績