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H D I N S I G H T S DNA double strand break is increased in striatal neurons of human HD patients.14 Lifespan elongation by Ku70. Double transgenic mice have a 30% longer lifespan.14 Colocalization of mutant huntingtin and Ku70 in a striatal neuron of R6/2 mouse.14 HD Research: Japan, cont... Moreover, mice models of HD treated with the above-mentioned genes have shown longer survival than other reported treatments. Due to limited social and financial support for HD research in Japan, HD research groups collaborate closely with each other and with research groups studying other neurodegenerative diseases. In order to advance HD research in Japan, there must be closer collaboration with researchers in countries that have a higher incidence of HD and consequent stronger support for HD research. International collaboration with pharmaceutical companies is also essential. Dr. Okazawa would like to thank all friends around the world for their current and future support. 1 Yazawa I, Nukina N, Hashida H, et al. Abnormal gene product identified in hereditary dentatorubralpallidoluysian atrophy (DRPLA) brain. Nat Genet 1995 May; 10(1):99-103. 6 Waragai M, Lammers CH, Takeuchi S, et al. PQBP-1, a novel polyglutamine tract-binding protein, inhibits transcription activation by Brn-2 and affects cell survival. Hum Mol Genet 1999 Jun;8(6):977-87. 11 Nagai Jana NR, Tanaka M, Wang GH, et al. Polyglutamine lengthdependent interaction of Hsp40 and Hsp70 family chaperones with truncated N-terminal huntingtin: their role in suppression of aggregation and cellular toxicity. Hum Mol Genet 2000 Aug;9(13):2009-18. 7 Okazawa 12 2 3 Bauer PO, Goswami A, Wong HK, et al. Harnessing chaperone-mediated autophagy for the selective degradation of mutant huntingtin protein. Nat Biotechnol 2010 Mar;28(3): 256-63. doi: 10.1038/nbt.1608. Epub 2010 Feb 28. 4 Matsumoto G, Wada K, Okuno M, et al. Serine 403 phosphorylation of p62/SQSTM1 regulates selective autophagic clearance of ubiquitinated proteins. Mol Cell 2011 Oct;44(2):279-89. Okamoto K, Okazawa H, Okuda A, et al. A novel octamer binding transcription factor is differentially expressed in mouse embryonic cells. Cell 1990 Feb;60(3):461-72. 5 8 H, Rich T, Chang A, et al. Interaction between mutant ataxin-1 and PQBP-1 affects transcription and cell death. Neuron 2002 May;34(5):701-13. VM, Freude K, Musante L, et al. Mutations in the polyglutamine binding protein 1 gene cause X-linked mental retardation. Nat Genet. 2003 Dec;35(4):313-5. Epub 2003 Nov 23. Y, Fujikake N, Ohno K, et al. Prevention of polyglutamine oligomerization and neurodegeneration by the peptide inhibitor QBP1 in Drosophila. Hum Mol Genet 2003 Jun;12(11):1253-9. Tagawa K, Marubuchi S, Qi ML, et al. The induction levels of heat shock protein 70 differentiate the vulnerabilities to mutant huntingtin among neuronal subtypes. J Neurosci 2007 Jan;27(4):868-80. 8 Kalscheuer M, Machida Y, Niu S, et al. Trehalose alleviates polyglutamine-mediated pathology in a mouse model of Huntington disease. Nat Med 2004 Feb;10(2):148-54. 13 Qi ML, Tagawa K, Enokido Y, et al. Proteome analysis of soluble nuclear proteins reveals that HMGB1/2 suppress genotoxic stress in polyglutamine diseases. Nat Cell Biol 2007 Apr;9(4):402-14. 9 Tanaka Nagai Y, Tucker T, Ren H, et al. Inhibition of polyglutamine protein aggregation and cell death by novel peptides identified by phage display screening. J Biol Chem 2000 Apr;275(14):10437-42. 14 Enokido Y, Tamura T, Ito H, et al. Mutant huntingtin impairs Ku70-mediated DNA repair. J Cell Biol 2010 May 3;189(3):425-43. 10 15 Fujita K, Nakamura Y, Oka T, et al. A functional deficiency of TERA/VCP/p97 contributes to impaired DNA damage repair in multiple polyglutamine diseases. Nature Commun In press. Copyright © Huntington Study Group 2013. All rights reserved. HD Insights, Vol. 4