Research Institute of Environmental Medicine Nagoya University

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Neuroscience and Pathobiology

Staff

Professor
Koji Yamanaka
Assistant Professor
Okiru Komine
Assistant Professor
Seiji Watanabe
Designated Assistant Professor
Akira Sobue
Designated Assistant Professor
Noe Kawade
member

Research Projects

The molecular mechanism of neurodegenerative diseases such as motor neuron disease (amyotrophic lateral sclerosis, ALS) remains unknown. Therefore, therapeutic strategy has not been established. Our laboratory aims to elucidate the mechanism of onset and progression of motor neuron disease, which have been shown to be derived from the pathological changes within different cell types; motor neurons and glial cells. We will analyze inherited ALS, using mouse, cell culture, and in vitro system as models. Based on these studies, we expect to design the therapeutic interventions for the sporadic ALS patients in future.

Selected Publications

  1. Sakai S, Watanabe S, Komine O, Sobue A, and Yamanaka K: Novel reporters of mitochondria-associated membranes (MAM), MAMtrackers, demonstrate MAM disruption as a common pathological feature in amyotrophic lateral sclerosis. The FASEB Journal e21688, 2021.
  2. Sobue A, Komine O, Hara Y, Endo F, Mizoguchi H, Watanabe S, Murayama S, Saito T, Saido T, Sahara N, Higuchi M, Ogi T and Yamanaka K: Microglial gene signature reveals loss of homeostatic microglia associated with neurodegeneration of Alzheimer's disease. Acta Neuropathologica Communications 9: 1, 2021.
  3. Watanabe S, Inami H, Oiwa K, Murata Y, Sakai S, Komine O, Sobue A, Iguchi Y, Katsuno M, Yamanaka K: Aggresome formation and liquid-liquid phase separation independently induce cytoplasmic aggregation of TAR DNA-binding protein 43. Cell Death & Disease11: 909, 2020.
  4. Watanabe S, Oiwa K, Murata Y, Komine O, Sobue A, Endo F, Takahashi E and Yamanaka K: ALS-linked TDP-43M337V knock-in mice exhibit splicing deregulation without neurodegeneration. Molecular Brain 13: 8, 2020.
  5. Nishino K, Watanabe S, Jin S, Murata Y, Oiwa K, Komine O, Endo F, Tsuiji H, Abe M, Sakimura K, Mishra A, Yamanaka K: Mice deficient in the C-terminal domain of TAR DNA-binding protein 43 develop age-dependent motor dysfunction associated with impaired Notch1-Akt signaling pathway. Acta Neuropathologica Communications 7(1): 118, 2019.
  6. 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.
  7. 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-beta1 accelerates disease progression in ALS mice by interfering with the neuroprotective functions of microglia and T cells. Cell Reports 11: 592, 2015.
  8. 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.
  9. 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.

(May 2, 2018)