名古屋大学環境医学研究所

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病態神経科学分野(病態神経科学

教員紹介

教授
YAMANAKA Koji
助教
KOMINE Okiru
助教
WATANABE Seiji
特任助教
SOBUE Akira
メンバー

研究内容

多くの遺伝性神経変性疾患の病因遺伝子が同定されていますが, その発症や疾患進行機序に関してはいまだ解明されていません. 当研究室では, 神経変性疾患の病態解明を目標として,特に筋萎縮性側索硬化症(ALS)とアルツハイマー病(AD)について研究を行っています. 当研究室でのこれまでの研究により, ALSの発症に必要な病的変化は運動ニューロンに起因し, 疾患の進行に関しては非神経細胞であるグリア細胞に起こる病的変化が寄与していることが明らかになりました. 当研究室では, 神経細胞内で起こる病的変化(タンパク質のフォールディングや分解の異常、RNA代謝異常など)とグリア細胞で起こる病的変化(神経炎症の異常など)の両面から神経変性疾患の病態を解明し, 新たな治療戦略を構築することを目指しています

研究実績

発表論文
  1. Komine O, Yamashita H, Fujimori-Tonou N, Koike M, Jin S, Moriwaki Y, Endo F, Watanabe S, Uematsu S, Akira S, Uchiyama Y, Takahashi R, Misawa H, Yamanaka K. Innate immune adaptor TRIF deficiency accelerates disease progression of ALS mice with accumulation of aberrantly activated astrocytes. Cell Death & Differentiation in press.
  2. Watanabe S, Komine O, Endo F, Wakasugi K, Yamanaka K. Intracerebroventricular administration of Cystatin C ameliorates disease in SOD1-linked amyotrophic lateral sclerosis mice. Journal of Neurochemistry 145: 80-89, 2018.
  3. Watanabe S, Ilieva H, Tamada H, Nomura H, Komine O, Endo F, Jin S, Mancias P, Kiyama H, Yamanaka K. Mitochondria-associated membrane collapse is a common pathomechanism in SIGMAR1- and SOD1-linked ALS. EMBO Mololecular Medicine 8(12): 1421-1437, 2016.
  4. Lasiene J, Komine O, Fujimori-Tonou N, Powers B, Endo F, Watanabe S, Shijie J, Ravits J, Horner P, Misawa H, Yamanaka K. Neuregulin 1 confers neuroprotection in SOD1-linked amyotrophic lateral sclerosis mice via restoration of C-boutons of spinal motor neurons. Acta Neuropathol Commun 4: 15, 2016.
  5. Endo F, Komine O, Fujimori-Tonou N, Jin S, Watanabe S, Katsuno M, Sobue G, Dezawa M, Wyss-Coray T, Yamanaka K. Astrocyte-derived TGF-β1 accelerates disease progression in ALS mice by interfering with the neuroprotective functions of microglia and T cells. Cell Reports 11: 592, 2015.
  6. Watanabe S, Ageta-Ishihara N, Nagatsu S, Takao K, Komine O, Endo F, Miyakawa T, Misawa H, Takahashi R, Kinoshita M, Yamanaka K. SIRT1 overexpression ameliorates a mouse model of SOD1-linked amyotrophic lateral sclerosis via HSF1/HSP70i chaperone system. Molecular Brain 7: 62, 2014.
  7. Austin JA, Wright GS, Watanabe S, Grossmann JG, Antonyuk SV, Yamanaka K, Hasnain SS. Disease causing mutants of TDP-43 nucleic acid binding domains are resistant to aggregation and have increased stability and half-life. Proceedings of the National Academy of Sciences of the United States of America 111: 4309-4314, 2014.
  8. Tsuiji H, Iguchi Y, Furuya A, Kataoka A, Hatsuta H, Atsuta N, Tanaka F, Hashizume Y, Akatsu H, Murayama S, Sobue G, Yamanaka K. Spliceosome Integrity is defective in Motor Neuron Diseases, ALS and SMA. EMBO Molecular Medicine 5: 221-234, 2013.
  9. Yamanaka K, Chun SJ, Boillee S, Fujimori-Tonou N, Yamashita H, Gutmann DH, Takahashi R, Misawa H, & Cleveland DW. Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis. Nature Neuroscience 11: 251-253, 2008.
  10. Boillee S, Yamanaka K, Lobsiger CS, Copeland NG, Jenkins NA, KassiotisG, KolliasG, Cleveland DW. Onset and Progression in Inherited ALS determined by Motor Neurons and Microglia. Science 312: 1389-1392, 2006.
著書・総説
  1. Yamanaka K, Komine O. The multi-dimensional roles of astrocytes in ALS. Neuroscience Research 126: 31-38, 2018.
  2. Endo F, Komine O, Yamanaka K. Neuroinflammation in motor neuron disease. Clinical and Experimental Neuroimmunology 7: 126-138, 2016.
  3. Heneka MT, Carson MJ, Khoury JE, Landreth GE, Brosseron F, Feinstein DL, Jacobs AH, Wyss-Coray T, Vitorica J, Ransohoff RM, Herrup K, Frautschy SA, Finsen B, Brown GC, Verkhratsky A, Yamanaka K, Koistinaho J, Latz E, Halle A, Petzold GC, Town T, Morgan D, Shinohara ML, Perry VH, Holmes C, Bazan NG, Brooks DJ, Hunot S, Joseph B, Deigendesch N, Garaschuk O, Boddeke E, Dinarello CA, Breitner JC, Cole GM, Golenbock DT, Kummer MP. Neuroinflammation in Alzheimer’s disease. Lancet Neurology 14: 388-405, 2015.
  4. 山中宏二. ミクログリアと神経変性疾患.Brain and Nerve 69: 999-1005, 2017.
  5. 山中宏二. 筋萎縮性側索硬化症と炎症 ―神経・免疫連関の立場から― 最新医学(最新医学社)71(2): 250- 255, 2016.