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Gen Sobue MD, PhDProfessor, Department of Neurology, Nagoya University Graduate School of Medicine


Specialized field

Neurology

Career Summary

1975
Graduated from Nagoya University School of Medicine (MD)
1981
Completed Nagoya University Graduate School of Medicine (PhD)
1981-1991
Lecturer, Aichi Medical University
1982-1983
Research Fellow, University of Pennsylvania
1983-1984
Assistant Professor, University of Pennsylvania
1991-1995
Associate Professor, Aichi Medical University
1995-2000
Professor, Nagoya University School of Medicine
2000-present
Professor, Nagoya University Graduate School of Medicine

Research Theme

Elucidation of pathogenesis and therapy development for neurodegenerative disorders

Research Summary

Spinal and bulbar muscular atrophy (SBMA) and amyotrophic lateral sclerosis (ALS) are adult-onset motor neuron diseases that represent neurodegenerative disorders. We have aimed at elucidation of pathogenesis and therapy development for these intractable diseases.
SBMA is a hereditary motor neuron disease caused by the expansion of a polyglutamine (polyQ) tract in the androgen receptor (AR). At present there are no treatments for SBMA, although leuprorelin suppressed the accumulation of pathogenic AR in a phase 2 trial. Recent functional studies have shown the potent activity of specific microRNAs (miRNAs) as disease modifiers both in vitro and in vivo. Thus, potential therapeutic approaches that target the miRNA processing pathway have recently attracted attention. In this study, we show a novel therapeutic approach using the adeno-associated virus (AAV) vector-mediated delivery of a specific miRNA for SBMA. We found that miR-196a enhanced the decay of the AR mRNA by silencing CUGBP, Elav-like family member 2 (CELF2). CELF2 directly acted on AR mRNA and enhanced the stability of AR mRNA. Furthermore, the early intervention of miR-196a delivered by an AAV vector ameliorated the symptomatic and histopathological phenotypes of SBMA in model mice. Our results indicate the potential for further research in the field of miRNA-mediated gene therapy for neurodegenerative disorders.
 Next, we assessed the efficacy and safety of leuprorelin for SBMA. A 48-week, randomized, double-blind, placebo-controlled trial was done at 14 hospitals. Patients with spinal and bulbar muscular atrophy were randomly assigned (1:1) by minimization to subcutaneous 11.25 mg leuprorelin or identical placebo every 12 weeks. Patients and investigators were masked to treatment allocation. The primary endpoint was pharyngeal barium residue, which indicates incomplete bolus clearance, measured at week 48 by videofluorography. All patients who were randomly assigned and who were assessed with videofluorography at least once were included in the analyses. 204 patients were randomly assigned and 199 started treatment: 100 with leuprorelin and 99 with placebo. At week 48, the pharyngeal barium residue after initial swallowing had changed by ?5?1% (SD 21.0) in the leuprorelin group and by 0?2% (18.2) in the placebo group (difference between groups ?5.3%; 95% CI ?10.8 to 0.3; p=0.063). The mean difference in pharyngeal barium residue after piecemeal deglutition at week 48 was ?3.2% (?6.4 to 0.0; p=0.049), but there was no significant difference between the groups after covariate adjustment for the baseline data (?4.1 to 1.6; p=0.392). In a predefined subgroup analysis, leuprorelin treatment was associated with a greater reduction in barium residue after initial swallowing than was placebo in patients with a disease duration less than 10 years (difference between groups ?9.8, ?17.1 to ?2.5; p=0.009). There were no significant differences in the number of drug-related adverse events between groups. To this end, 48 weeks of treatment with leuprorelin did not show significant effects on swallowing function in patients with SBMA, although it was well tolerated. Disease duration might influence the efficacy of leuprorelin and thus further clinical trials with sensitive outcome measures should be done in subpopulations of patients.
TAR DNA-binding protein 43 kDa (TDP-43) is a major component of ubiquitin-positive inclusion of TDP-43 proteinopathies including ALS and frontotemporal lobar degeneration with ubiquitinated inclusions, which is now referred to as FTLD-TDP. TDP-43 in the aberrant inclusion is known to be hyperphosphorylated at C-terminal sites, to be truncated at the N-terminal region, and to re-distribute from nucleus to cytoplasm or neurite. The pathogenic role of these modifications, however, has not been clarified. TDP-43 redistributes to cytoplasm and forms aggregates which is the histopathological hallmark of sporadic ALS (SALS) in affected motor neurons, suggesting loss of TDP-43 function causes the neurodegeneration. To test this hypothesis, we generated motor neuron-specific TDP-43 knockout (TDP CKO) mice. TDP CKO mice developed progressive weight loss and motor impairment around the age of 60 weeks. Pathological analyses showed progressive atrophy in TDP-43-lacking spinal motor neurons, loss of large myelinated fibers in the ventral root, grouped atrophy of the skeletal muscle, and denervation in the neuromuscular junction; whereas, extraocular motor neurons, that are essentially resistant in ALS remained preserved. Additionally, ultra structural analysis revealed autolysosomes and autophagosomes in motor neurons of TDP CKO mice. In summary, TDP CKO mice exhibited age-dependent motor dysfunction accompanied by neuropathological alterations, that simulate symptomatic and pathological feature of SALS. These findings suggest that TDP-43 plays an essential role in the long term maintenance of motor neurons, and that loss of TDP-43 function contributes to the pathogenesis of ALS.

Principal Research Achievement

  1. Miyazaki Y, Adachi H, Katsuno M, Minamiyama M, Jiang YM, Huang Z, Doi H, Matsumoto S, Kondo N, Iida M, Tohnai G, Tanaka F, Muramatsu S, Sobue G: Viral delivery of miR-196a ameliorates the SBMA phenotype via the silencing of CELF2. Nat Med, in press (2012)
  2. Tanaka F, Ikenaka K, Yamamoto M, Sobue G: Neuropathology and omics in motor neuron diseases. Neuropathology, in press (2012)
  3. Hama T, Hirayama M, Hara T, Nakamura T, Atsuta N, Banno H, Suzuki K, Katsuno M, Tanaka F, Sobue G: Discrimination of spinal and bulbar muscular atrophy from amyotrophic lateral sclerosis using sensory nerve action potentials. Muscle Nerve, 45, 169-174 (2012)
  4. Katsuno M, Tanaka F, Sobue G: Perspectives on molecular targeted therapies and clinical trials for neurodegenerative diseases. J Neurol Neurosurg Psychiatry, 83, 329-335 (2012)
  5. Katsuno M, Banno H, Suzuki K, Adachi H, Tanaka F, Sobue G: Molecular pathophysiology and disease-modifying therapies for spinal and bulbar muscular atrophy. Arch Neurol, 69, 436-440 (2012)
  6. Hashizume A, Watanabe H, Matsuo K, Katsuno M, Tanaka F, Nagatani T, Sobue G: Endoscopic third ventriculotomy improves Parkinsonism following a ventriculo-peritoneal shunt in a patient with non communicating hydrocephalus secondary to idiopathic aqueduct stenosis. J Neurol Sci, 309, 148-150 (2011)
  7. Hoshino T, Murao N, Namba T, Takehara M, Adachi H, Katsuno M, Sobue G, Matsushima T, Suzuki T, Mizushima T: Suppression of Alzheimer's disease-related phenotypes by expression of heat shock protein 70 in mice. J Neurosci, 31, 5225-5234 (2011)
  8. Iida A, Takahashi A, Kubo M, Saito S, Hosono N, Ohnishi Y, Kiyotani K, Mushiroda T, Nakajima M, Ozaki K, Tanaka T, Tsunoda T, Oshima S, Sano M, Kamei T, Tokuda T, Aoki M, Hasegawa K, Mizoguchi K, Morita M, Takahashi Y, Katsuno M, Atsuta N, Watanabe H, Tanaka F, Kaji R, Nakano I, Kamatani N, Tsuji S, Sobue G, Nakamura Y, Ikegawa S: A functional variant in ZNF512B is associated with susceptibility to amyotrophic lateral sclerosis in Japanese. Hum Mol Genet, 20, 3684-3692 (2011)
  9. Morozumi S, Koike H, Tomita M, Kawagashira Y, Iijima M, Katsuno M, Hattori N, Tanaka F, Sobue G: Spatial distribution of nerve fiber pathology and vasculitis in microscopic polyangiitis-associated neuropathy. J Neuropathol Exp Neurol, 70, 340-348 (2011)
  10. Takeuchi H, Mizoguchi H, Doi Y, Jin S, Noda M, Liang J, Li H, Zhou Y, Mori R, Yasuoka S, Li E, Parajuli B, Kawanokuchi J, Sonobe Y, Sato J, Yamanaka K, Sobue G, Mizuno T, Suzumura A: Blockade of gap junction hemichannel suppresses disease progression in mouse models of amyotrophic lateral sclerosis and Alzheimer's disease. PLoS One, 6, e21108 (2011)
  11. Yu Z, Wang AM, Adachi H, Katsuno M, Sobue G, Yue Z, Robins DM, Lieberman AP: Macroautophagy is regulated by the UPR-mediator CHOP and accentuates the phenotype of SBMA mice. PLoS Genet, 7, e1002321 (2011)
  12. Sone J, Tanaka F, Koike H, Inukai A, Katsuno M, Yoshida M, Watanabe H and Sobue G: Skin biopsy is useful for the antemortem diagnosis of neuronal intranuclear inclusion disease. Neurology, 76, 1372-1376 (2011)
  13. Senda J, Kato S, Kaga T, Ito M, Atsuta N, Nakamura T, Watanabe H, Tanaka F, Naganawa S and Sobue G: Progressive and widespread brain damage in ALS: MRI voxel-based morphometry and diffusion tensor imaging study. Amyotroph Lateral Scler, 12, 59-69 (2011)
  14. Miyazaki Y, Koike H, Ito M, Atsuta N, Watanabe H, Katsuno M, Kusunoki S and Sobue G: Acute superficial sensory neuropathy with generalized anhidrosis, anosmia, and ageusia. Muscle Nerve, 43, 286-288 (2011)
  15. Katsuno M, Adachi H, Banno H, Suzuki K, Tanaka F and Sobue G: Transforming growth factor-beta signaling in motor neuron diseases. Curr Mol Med, 11, 48-56 (2011)
  16. Iida A, Takahashi A, Deng M, Zhang Y, Wang J, Atsuta N, Tanaka F, Kamei T, Sano M, Oshima S, Tokuda T, Morita M, Akimoto C, Nakajima M, Kubo M, Kamatani N, Nakano I, Sobue G, Nakamura Y, Fan D and Ikegawa S: Replication analysis of SNPs on 9p21.2 and 19p13.3 with amyotrophic lateral sclerosis in East Asians. Neurobiol Aging, 32, 757 e713-754 (2011)
  17. Hirayama M, Nakamura T, Watanabe H, Uchida K, Hama T, Hara T, Niimi Y, Ito M, Ohno K and Sobue G: Urinary 8-hydroxydeoxyguanosine correlate with hallucinations rather than motor symptoms in Parkinson's disease. Parkinsonism Relat Disord, 17, 46-49 (2011)
  18. Hashizume A, Koike H, Kawagashira Y, Banno H, Suzuki K, Ito M, Katsuno M, Watanabe H, Tanaka F, Naganawa S, Kaneko R, Ishii A and Sobue G: Central nervous system involvement in n-hexane polyneuropathy demonstrated by MRI and proton MR spectroscopy. Clin Neurol Neurosurg, (2011)
  19. Banno H, Katsuno M, Suzuki K and Sobue G: Dutasteride for spinal and bulbar muscular atrophy. Lancet Neurol, 10, 113-115 (2011)
  20. Yamashita F, Hirayama M, Nakamura T, Takamori M, Hori N, Uchida K, Hama T and Sobue G: Pupillary autonomic dysfunction in multiple system atrophy and Parkinson's disease: an assessment by eye-drop tests. Clin Auton Res, 20, 191-197 (2010)
  21. Watanabe H, Ito M, Fukatsu H, Senda J, Atsuta N, Kaga T, Kato S, Katsuno M, Tanaka F, Hirayama M, Naganawa S and Sobue G: Putaminal magnetic resonance imaging features at various magnetic field strengths in multiple system atrophy. Mov Disord, 25, 1916-1923 (2010)
  22. Ukai K, Matsuo K, Nakamura R, Sobue G, Kosaka K, Shibayama H, Iritani S, Ishihara R and Ozaki N: A case of dementia with Lewy bodies that temporarily showed symptoms similar to Creutzfeldt-Jakob disease. Psychogeriatrics, 10, 201-205 (2010)
  23. Tomita M, Watanabe H, Morozumi S, Kawagashira Y, Iijima M, Nakamura T, Katsuno M, Koike H, Hattori N, Hirayama M, Kusunoki S and Sobue G: Pyramidal tract involvement in Guillain-Barre syndrome associated with anti-GM1 antibody. J Neurol Neurosurg Psychiatry, 81, 583-585 (2010)
  24. Takazawa T, Ikeda K, Hirayama T, Kawabe K, Nakamura Y, Ito H, Kano O, Yoshii Y, Tanaka F, Sobue G and Iwasaki Y: Familial amyotrophic lateral sclerosis with a novel G85S mutation of superoxide dismutase 1 gene: clinical features of lower motor neuron disease. Intern Med, 49, 183-186 (2010)
  25. Suzuki K, Katsuno M, Banno H, Takeuchi Y, Kawashima M, Suga N, Hashizume A, Hama T, Uchida K, Yamashita F, Nakamura T, Hirayama M, Tanaka F and Sobue G: The profile of motor unit number estimation (MUNE) in spinal and bulbar muscular atrophy. J Neurol Neurosurg Psychiatry, 81, 567-571 (2010)
  26. Sone J, Niwa J, Kawai K, Ishigaki S, Yamada S, Adachi H, Katsuno M, Tanaka F, Doyu M and Sobue G: Dorfin ameliorates phenotypes in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurosci Res, 88, 123-135 (2010)

  27. Senda J, Ito M, Atsuta N, Watanabe H, Hattori N, Kawai H and Sobue G: Paradoxical brain embolism induced by Mycoplasma pneumoniae infection with deep venous thrombus. Intern Med, 49, 2003-2005 (2010)
  28. Ohgami N, Ida-Eto M, Shimotake T, Sakashita N, Sone M, Nakashima T, Tabuchi K, Hoshino T, Shimada A, Tsuzuki T, Yamamoto M, Sobue G, Jijiwa M, Asai N, Hara A, Takahashi M and Kato M: c-Ret-mediated hearing loss in mice with Hirschsprung disease. Proc Natl Acad Sci U S A, 107, 13051-13056 (2010)
  29. Nakamura T, Hirayama M, Yamashita F, Uchida K, Hama T, Watanabe H and Sobue G: Lowered cardiac sympathetic nerve performance in response to exercise in Parkinson's disease. Mov Disord, 25, 1183-1189 (2010)
  30. Mo K, Razak Z, Rao P, Yu Z, Adachi H, Katsuno M, Sobue G, Lieberman AP, Westwood JT and Monks DA: Microarray analysis of gene expression by skeletal muscle of three mouse models of Kennedy disease/spinal bulbar muscular atrophy. PLoS One, 5, e12922 (2010)
  31. Matsuda M, Hoshino T, Yamashita Y, Tanaka K, Maji D, Sato K, Adachi H, Sobue G, Ihn H, Funasaka Y and Mizushima T: Prevention of UVB radiation-induced epidermal damage by expression of heat shock protein 70. J Biol Chem, 285, 5848-5858 (2010)
  32. Koike H and Sobue G: Expanding the concept of inflammatory neuropathies. Brain, 133, 2848-2851 (2010)
  33. Koike H, Koyano S, Morozumi S, Kawagashira Y, Iijima M, Katsuno M, Hattori N, Vernino S and Sobue G: Slowly progressive autonomic neuropathy with antiganglionic acetylcholine receptor antibody. J Neurol Neurosurg Psychiatry, 81, 586-587 (2010)
  34. Koike H, Kiuchi T, Iijima M, Ueda M, Ando Y, Morozumi S, Tomita M, Kawagashira Y, Watanabe H, Katsuno M, Shimoyama Y, Okazaki Y, Kamei H and Sobue G: Systemic but asymptomatic transthyretin amyloidosis 8 years after domino liver transplantation. J Neurol Neurosurg Psychiatry, (2010)
  35. Koike H, Atsuta N, Adachi H, Iijima M, Katsuno M, Yasuda T, Fukada Y, Yasui K, Nakashima K, Horiuchi M, Shiomi K, Fukui K, Takashima S, Morita Y, Kuniyoshi K, Hasegawa Y, Toribe Y, Kajiura M, Takeshita S, Mukai E and Sobue G: Clinicopathological features of acute autonomic and sensory neuropathy. Brain, 133, 2881-2896 (2010)
  36. Kawagashira Y, Watanabe H, Morozumi S, Iijima I, Koike H, Hattori N and Sobue G: Differential response to intravenous immunoglobulin (IVIg) therapy among multifocal and polyneuropathy types of painful diabetic neuropathy. J Clin Neurosci, 17, 1003-1008 (2010)
  37. Kawagashira Y, Kondo N, Atsuta N, Iijima M, Koike H, Katsuno M, Tanaka F, Kusunoki S and Sobue G: IgM MGUS anti-MAG neuropathy with predominant muscle weakness and extensive muscle atrophy. Muscle Nerve, 42, 433-435 (2010)
  38. Kawagashira Y, Koike H, Tomita M, Morozumi S, Iijima M, Nakamura T, Katsuno M, Tanaka F and Sobue G: Morphological progression of myelin abnormalities in IgM-monoclonal gammopathy of undetermined significance anti-myelin-associated glycoprotein neuropathy. J Neuropathol Exp Neurol, 69, 1143-1157 (2010)
  39. Katsuno M, Banno H, Suzuki K, Takeuchi Y, Kawashima M, Yabe I, Sasaki H, Aoki M, Morita M, Nakano I, Kanai K, Ito S, Ishikawa K, Mizusawa H, Yamamoto T, Tsuji S, Hasegawa K, Shimohata T, Nishizawa M, Miyajima H, Kanda F, Watanabe Y, Nakashima K, Tsujino A, Yamashita T, Uchino M, Fujimoto Y, Tanaka F and Sobue G: Efficacy and safety of leuprorelin in patients with spinal and bulbar muscular atrophy (JASMITT study): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol, 9, 875-884 (2010)
  40. Katsuno M, Banno H, Suzuki K, Adachi H, Tanaka F and Sobue G: Clinical features and molecular mechanisms of spinal and bulbar muscular atrophy (SBMA). Adv Exp Med Biol, 685, 64-74 (2010)
  41. Katsuno M, Adachi H, Minamiyama M, Waza M, Doi H, Kondo N, Mizoguchi H, Nitta A, Yamada K, Banno H, Suzuki K, Tanaka F and Sobue G: Disrupted transforming growth factor-beta signaling in spinal and bulbar muscular atrophy. J Neurosci, 30, 5702-5712 (2010)
  42. Kato T, Emi M, Sato H, Arawaka S, Wada M, Kawanami T, Katagiri T, Tsuburaya K, Toyoshima I, Tanaka F, Sobue G and Matsubara K: Segmental copy-number gain within the region of isopentenyl diphosphate isomerase genes in sporadic amyotrophic lateral sclerosis. Biochem Biophys Res Commun, 402, 438-442 (2010)
  43. Katada E, Nakamura T, Watanabe H, Matsukawa N, Ojika K and Sobue G: [Lambert-Eaton myasthenic syndrome associated with pulmonary squamous cell carcinoma and circulating anti-P/Q-type voltage-gated calcium channel antibody]. Rinsho Shinkeigaku, 50, 17-19 (2010)
  44. Hoshino T, Matsuda M, Yamashita Y, Takehara M, Fukuya M, Mineda K, Maji D, Ihn H, Adachi H, Sobue G, Funasaka Y and Mizushima T: Suppression of melanin production by expression of HSP70. J Biol Chem, 285, 13254-13263 (2010)
  45. Collins MP, Dyck PJ, Gronseth GS, Guillevin L, Hadden RD, Heuss D, Leger JM, Notermans NC, Pollard JD, Said G, Sobue G, Vrancken AF and Kissel JT: Peripheral Nerve Society Guideline on the classification, diagnosis, investigation, and immunosuppressive therapy of non-systemic vasculitic neuropathy: executive summary. J Peripher Nerv Syst, 15, 176-184 (2010)
  46. Iijima M, Tomita M, Morozumi S, Kawagashira Y, Nakamura T, Koike H, Katsuno M, Hattori N, Tanaka F, Yamamoto M, Sobue G. Single nucleotide polymorphism of TAG-1 influences IVIg responsiveness of Japanese patients with CIDP. Neurology, 73, 1348-1352 (2009)
  47. Palazzolo I, Stack C, Kong L, Musaro A, Adachi H, Katsuno M, Sobue G, Taylor JP, Sumner CJ, Fischbeck KH, Pennuto M. Overexpression of IGF-1 in muscle attenuates disease in a mouse model of spinal and bulbar muscular atrophy. Neuron, 63, 316-328 (2009)
  48. Sone J, Niwa JI, Kawai K, Ishigaki S, Yamada SI, Adachi H, Katsuno M, Tanaka F, Doyu M, Sobue G. Dorfin ameliorates phenotypes in a transgenic mouse model of amyotrophic lateral sclerosis. J Neurosci Res, 88, 123-135 (2009)
  49. Iguchi Y, Katsuno M, Niwa J, Yamada S, Sone J, Waza M, Adachi H, Tanaka F, Nagata K, Arimura N, Watanabe T, Kaibuchi K, Sobue G. TDP-43 depletion induces neuronal cell damage through dysregulation of Rho family GTPases. J Biol Chem, 284, 22059-22066 (2009)
  50. Suemasu S, Tanaka K, Namba T, Ishihara T, Katsu T, Fujimoto M, Adachi H, Sobue G, Takeuchi K, Nakai A, Mizushima T. A role for HSP70 in protecting against indomethacin-induced gastric lesions. J Biol Chem, 284, 19705-19715 (2009)
  51. Katsuno M, Adachi H, Sobue G. Getting a handle on Huntington's disease: the case for cholesterol. Nature Med, 15, 253-254 (2009)
  52. Banno H, Katsuno M, Suzuki K, Takeuchi Y, Kawashima M, Suga N, Takamori M, Ito M, Nakamura T, Matsuo K, Yamada S, Oki Y, Adachi H, Minamiyama M, Waza M, Atsuta N, Watanabe H, Fujimoto Y, Nakashima T, Tanaka F, Doyu M, Sobue G. Phase 2 trial of leuprorelin in patients with spinal and bulbar muscular atrophy. Ann Neurol, 65, 140-150 (2009)
  53. Watanabe H, Hirayama M, Noda A, Ito M, Atsuta N, Senda J, Kaga T, Yamada A, Katsuno M, Niwa T, Tanaka F, Sobue G. B-type natriuretic peptide and cardiovalvulopathy in Parkinson disease with dopamine agonist. Neurology, 72, 621-626 (2009)
  54. Tokui K, Adachi H, Waza M, Katsuno M, Minamiyama M, Doi H, Tanaka K, Hamazaki J, Murata S, Tanaka F, Sobue G. 17-DMAG ameliorates polyglutamine-mediated motor neuron degeneration through well-preserved proteasome function in an SBMA model mouse. Hum Mol Genet, 18, 898-910 (2009)
  55. Okada Y, Matsumoto A, Shimazaki T, Enoki R, Koizumi A, Ishii S, Itoyama Y, Sobue G, Okano H. Spatiotemporal recapitulation of central nervous system development by murine embryonic stem cell-derived neural stem/progenitor cells. Stem Cells, 26, 3086-3098 (2008)
  56. Kawai Y, Suenaga M, Takeda A, Ito M, Watanabe H, Tanaka F, Kato K, Fukatsu H, Naganawa S, Kato T, Ito K, Sobue G. Cognitive impairments in multiple system atrophy: MSA-C vs MSA-P. Neurology, 70, 1390-1396 (2008)
  57. Suzuki K, Katsuno M, Banno H, Takeuchi Y, Atsuta N, Ito M, Watanabe H, Yamashita F, Hori N, Nakamura T, Hirayama M, Tanaka F, Sobue G. CAG repeat size correlates to electrophysiological motor and sensory phenotypes in SBMA. Brain, 131, 229-239 (2008)
  58. Okada Y et al. Spatio-temporal recapitulation of central nervous system development by murine ES cell-derived neural stem/progenitor cells. Stem Cells in press (2008)
  59. Yang Z et al. ASC-J9 ameliorates spinal and bulbar muscular atrophy phenotype via degradation of androgen receptor. Nature Med. 13: 348-353 (2007)
  60. Adachi H et al. CHIP overexpression reduces mutant androgen receptor protein and ameliorates phenotypes of the spinal and bulbar muscular atrophy transgenic mouse model. J. Neurosci. 27: 5115-5126 (2007)
  61. Katsumo M et al. Reversible disruption of dynactin 1-mediated retrograde axonal transport in polyglutamine-induced motor neuron degeneration. J. Neurosci. 26: 12106-12117 (2006)
  62. Banno H et al. Mutant androgen receptor accumulation in spinal and bulbar muscular atrophy scrotal skin: a pathogenic marker. Ann. Neurol. 59: 520-526 (2006)
  63. Waza M et al. 17-AAG, an Hsp90 inhibitor, ameliorates polyglutamine-mediated motor neuron degeneration. Nature Med. 11: 1088-1095 (2005)
  64. Katsuno M et al. Pharmacological induction of heat shock proteins alleviates polyglutamine-mediated motor neuron disease. Proc. Natl. Acad. Sci. USA. 102: 16801-16806 (2005)
  65. Jiang YM et al. Gene expression profile of motor neurons in sporadic amyotrophic lateral sclerosis. Ann. Neurol. 57: 236-251 (2005)
  66. Katsuno M et al. Sweet relief for Huntington’s disease. Nature Med. 10: 123 (2004)
  67. Katsuno M et al. Polyglutamine diminishes VEGF: Passage to motor neuron death? Neuron 41: 677-679 (2004)
  68. Katsuno M et al. Leuprorelin rescue polyglutamine-dependent phenotypes in a transgenic mouse model of spinal and bulbar muscular atrophy. Nature Med. 9: 768-773 (2003)
  69. Katsuno M et al. Teststerone reduction prevents phenotypic expression in a transgenic mouse model of spinal and bulbar muscular atrophy. Neuron 35: 843-854 (2002)
  70. Hashimoto Y et al. A rescue factor abolishing neuronal cell death by a wide spectrum of familial Alzheimer’s disease genes and Aβ. Proc. Natl. Acad. Sci. USA. 98: 6336-6341 (2001)
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  72. Inoue H et al. A gene encoding a transmembrane protein is mutated in patients with diabates mellitus and optic atrophy (Wolfram syndrome). Nature Genet. 20: 143-148 (1998)
  73. Kawakami H et al. Unique features of the CAG repeats in Machado-Joseph disease. Nature Genet. 9: 344-345 (1995)
  74. Sobue G et al. Schwann cell galactocerebroside induced by derivatives of adenosine 3’, 5’- monophosphate. Science 224: 72-74 (1984)

Award

Toshihiko Tokizane Memorial Award 2005
Chunichi Culture Award 2007

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