Laboratory for Motor Neuron Disease

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.

Research Subjects

• The role of glial cells in disease progression of ALS.
• To elucidate the roles of protein and RNA quality control in neurodegenerative diseases.
• Uncovering molecular machinery essential for the survival of motor neurons through generating new mouse model for ALS.

Publications

1. 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 Mol. Med. 5: 221-234, (2013).
2. Watanabe S, Kaneko K, Yamanaka K.:
   "Accelerated disease onset with stabilized familial amyotrophic lateral sclerosis (ALS)-linked mutant TDP-43 proteins. "
   J Biol. Chem. 288: 3641-3654, (2013).
3. Mishra A, Maheshwari M, Chhangani D, Fujimori-Tonou N, Endo, F, Joshi AP, Jana NR, Yamanaka K.:
   "E6-AP association promotes SOD1 aggresomes degradation and suppresses toxicity."
   Neurobiol Aging, 34:1310.e11-23, (2013).
4. Israelson A, Arbel N, Da Cruz S, Ilieva H, Yamanaka K, Shoshan-Barmatz V, Clevalend DW.:
   "Misfolded Mutant SOD1 Directly Inhibits VDAC1 Conductance in a Mouse Model of Inherited ALS."
   Neuron, 67: 575-87, (2010).
5. Lobsiger CS, Boillee S, McAlonis-Downes M, Khan AM, Feltri ML, Yamanaka K, Cleveland DW.:
   "Schwann cells expressing dismutase active mutant SOD1 unexpectedly slow disease progression in ALS mice."
   Proc. Natl. Acad. Sci., USA, 106: 4465-70, (2009).
6. Yamanaka K, Boillee S, Roberts EA, Garcia ML, McAlonis-Downes M, Mikse OR, Cleveland DW, 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).
7. 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."
   Nat. Neurosci., 11, 251-253 (2008).
8. Yamashita H, Kawamata J, Okawa K, Kanki R, Nakamizo T, Hatayama T, Yamanaka K, Takahashi R, 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)
9. Boillee, S., Yamanaka, K., Lobsiger, CS., Copeland, NG., Jenkins, NA., Kassiotis, G., Kollias, G., Cleveland, DW.:
   "Onset and Progression in Inherited ALS determined by Motor Neurons and Microglia"
   Science, 312, 1389-1392 (2006).
10. Yamanaka, K., Miller, TM., McAlonis-Downes, M., Chun, SJ., Cleveland, DW.:
    "Progressive axonal degeneration and slowness in ALS2-deficient mice"
    Ann. Neurol., 60, 95-104 (2006).