Laboratory for Motor Neuron Disease
Research Areas
| The molecular mechanism of neurodegenerative diseases such as motor neuron disease (amyotrophic lateral sclerosis, ALS) remains unknown. Therefore, therapeutic strategy has not been established. The aim of our research unit is 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. |  Laboratory Head Koji YAMANAKA (M.D., Ph.D.)  |
Research Subjects
| (1) | To elucidate the alteration of protein quality control and protein localization in inherited ALS model |
| (2) | The role of glial cells in disease progression of ALS |
| (3) | Molecular machinery which is essential for the survival of motor neurons |
List of Selected Publications
| (1) | Yamanaka, K., Boillee, S., Roberts, EA., Garcia, ML., McAlonis-Downes, M., Mikse, OR., Cleveland, DW., and Goldstein, LSB.: "Mutant SOD1 in cell types other than motor neurons and oligodendrocytes accelerates onset of disease in ALS mice." Proc. Natl. Acad. Sci., USA, 105: 7594-7599, (2008). |
| (2) | Yamanaka, K., Chun SJ., Boillee, S., Fujimori-Tonou, N., Yamashita, H., Gutmann DH., Takahashi, R., Misawa, H., and Cleveland, DW.: "Astrocytes as determinants of disease progression in inherited amyotrophic lateral sclerosis." Nature Neuroscience, 11, 251-253 (2008). |
| (3) | Yamashita, H., Kawamata, J., Okawa, K., Kanki, R., Nakamizo, T., Hatayama, T., Yamanaka, K., Takahashi, R., and Shimohama, S.: "Heat-shock protein 105 interacts with and suppresses aggregation of mutant Cu/Zn superoxide dismutase; clues to a possible strategy for treating ALS." J. Neurochem., 102, 1497-1505 (2007) |
| (4) | Boillee, S., Yamanaka, K., Lobsiger, CS., Copeland, NG., Jenkins, NA., Kassiotis, G., Kollias, G., and Cleveland, DW.: "Onset and Progression in Inherited ALS determined by Motor Neurons and Microglia." Science, 312, 1389-1392 (2006). |
| (5) | Yamanaka, K., Miller, TM., McAlonis-Downes, M., Chun, SJ., and Cleveland, DW.: "Progressive axonal degeneration and slowness in ALS2-deficient mice." Ann. Neurol., 60, 95-104 (2006). |
| (6) | Miller, TM., Kim, SH., Yamanaka, K., Hester, M., Umapathi, P., Arnson, H., Rizo, L., Mendell, JR., Gage, FH., Cleveland, DW., and Kaspar, BK.: "Gene transfer demonstrates that muscle is not a primary target for non-cell autonomous toxicity in familial amyotrophic lateral sclerosis." Proc. Natl. Acad. Sci. USA, 103, 19546-19551 (2006). |
| (7) | Smith, RA., Miller, TM., Yamanaka, K., Monia, BP., Condon, TP., Hung, G., Lobsiger, CS., Ward, CM., McAlonis-Downes, M., Wei, H., Wancewicz, EV., Bennett, CF., and Cleveland, DW.: "Antisense Oligonucleotides as a Therapy for Neurodegenerative diseases." J. Clin. Invest., 116, 2290-2296 (2006). |
| (8) | Yamanaka, K., VandeVelde, C., Eymard-Pierre, E., Bertini, E., Boespflug-Tanguy, O., and Cleveland, DW.: "Unstable mutants in the peripheral endosomal membrane component ALS2 cause early onset motor neuron disease." Proc. Natl. Acad. Sci. USA, 100, 16041-16046 (2003). |
| (9) | Yamanaka, K., Ishikawa, H., Megumi, Y., Tokunaga, F., Kanie, M., Rouault, TA., Morishima, I., Minato, N., Ishimori, K., and Iwai, K.: "Identification of the ubiquitin-protein ligase that recognizes oxidized IRP2." Nat. Cell Biol., 5, 336-340 (2003). |