Neuroscience and Pathobiology
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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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)