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American Journal of Human Genetics logoLink to American Journal of Human Genetics
. 1999 Feb;64(2):339–345. doi: 10.1086/302269

Protein fate in neurodegenerative proteinopathies: polyglutamine diseases join the (mis)fold.

H L Paulson 1
PMCID: PMC1377742  PMID: 9973270

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Selected References

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  1. Becher M. W., Kotzuk J. A., Sharp A. H., Davies S. W., Bates G. P., Price D. L., Ross C. A. Intranuclear neuronal inclusions in Huntington's disease and dentatorubral and pallidoluysian atrophy: correlation between the density of inclusions and IT15 CAG triplet repeat length. Neurobiol Dis. 1998 Apr;4(6):387–397. doi: 10.1006/nbdi.1998.0168. [DOI] [PubMed] [Google Scholar]
  2. Cooper J. K., Schilling G., Peters M. F., Herring W. J., Sharp A. H., Kaminsky Z., Masone J., Khan F. A., Delanoy M., Borchelt D. R. Truncated N-terminal fragments of huntingtin with expanded glutamine repeats form nuclear and cytoplasmic aggregates in cell culture. Hum Mol Genet. 1998 May;7(5):783–790. doi: 10.1093/hmg/7.5.783. [DOI] [PubMed] [Google Scholar]
  3. Cummings C. J., Mancini M. A., Antalffy B., DeFranco D. B., Orr H. T., Zoghbi H. Y. Chaperone suppression of aggregation and altered subcellular proteasome localization imply protein misfolding in SCA1. Nat Genet. 1998 Jun;19(2):148–154. doi: 10.1038/502. [DOI] [PubMed] [Google Scholar]
  4. Davies S. W., Turmaine M., Cozens B. A., DiFiglia M., Sharp A. H., Ross C. A., Scherzinger E., Wanker E. E., Mangiarini L., Bates G. P. Formation of neuronal intranuclear inclusions underlies the neurological dysfunction in mice transgenic for the HD mutation. Cell. 1997 Aug 8;90(3):537–548. doi: 10.1016/s0092-8674(00)80513-9. [DOI] [PubMed] [Google Scholar]
  5. DiFiglia M., Sapp E., Chase K. O., Davies S. W., Bates G. P., Vonsattel J. P., Aronin N. Aggregation of huntingtin in neuronal intranuclear inclusions and dystrophic neurites in brain. Science. 1997 Sep 26;277(5334):1990–1993. doi: 10.1126/science.277.5334.1990. [DOI] [PubMed] [Google Scholar]
  6. Goldberg Y. P., Nicholson D. W., Rasper D. M., Kalchman M. A., Koide H. B., Graham R. K., Bromm M., Kazemi-Esfarjani P., Thornberry N. A., Vaillancourt J. P. Cleavage of huntingtin by apopain, a proapoptotic cysteine protease, is modulated by the polyglutamine tract. Nat Genet. 1996 Aug;13(4):442–449. doi: 10.1038/ng0896-442. [DOI] [PubMed] [Google Scholar]
  7. Hardy J., Gwinn-Hardy K. Genetic classification of primary neurodegenerative disease. Science. 1998 Nov 6;282(5391):1075–1079. doi: 10.1126/science.282.5391.1075. [DOI] [PubMed] [Google Scholar]
  8. Hodges M., Tissot C., Howe K., Grimwade D., Freemont P. S. Structure, organization, and dynamics of promyelocytic leukemia protein nuclear bodies. Am J Hum Genet. 1998 Aug;63(2):297–304. doi: 10.1086/301991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Holmberg M., Duyckaerts C., Dürr A., Cancel G., Gourfinkel-An I., Damier P., Faucheux B., Trottier Y., Hirsch E. C., Agid Y. Spinocerebellar ataxia type 7 (SCA7): a neurodegenerative disorder with neuronal intranuclear inclusions. Hum Mol Genet. 1998 May;7(5):913–918. doi: 10.1093/hmg/7.5.913. [DOI] [PubMed] [Google Scholar]
  10. Hong M., Zhukareva V., Vogelsberg-Ragaglia V., Wszolek Z., Reed L., Miller B. I., Geschwind D. H., Bird T. D., McKeel D., Goate A. Mutation-specific functional impairments in distinct tau isoforms of hereditary FTDP-17. Science. 1998 Dec 4;282(5395):1914–1917. doi: 10.1126/science.282.5395.1914. [DOI] [PubMed] [Google Scholar]
  11. Huynh D. P., Del Bigio M. R., Ho D. H., Pulst S. M. Expression of ataxin-2 in brains from normal individuals and patients with Alzheimer's disease and spinocerebellar ataxia 2. Ann Neurol. 1999 Feb;45(2):232–241. doi: 10.1002/1531-8249(199902)45:2<232::aid-ana14>3.0.co;2-7. [DOI] [PubMed] [Google Scholar]
  12. Ikeda H., Yamaguchi M., Sugai S., Aze Y., Narumiya S., Kakizuka A. Expanded polyglutamine in the Machado-Joseph disease protein induces cell death in vitro and in vivo. Nat Genet. 1996 Jun;13(2):196–202. doi: 10.1038/ng0696-196. [DOI] [PubMed] [Google Scholar]
  13. Jackson G. R., Salecker I., Dong X., Yao X., Arnheim N., Faber P. W., MacDonald M. E., Zipursky S. L. Polyglutamine-expanded human huntingtin transgenes induce degeneration of Drosophila photoreceptor neurons. Neuron. 1998 Sep;21(3):633–642. doi: 10.1016/s0896-6273(00)80573-5. [DOI] [PubMed] [Google Scholar]
  14. Kitada T., Asakawa S., Hattori N., Matsumine H., Yamamura Y., Minoshima S., Yokochi M., Mizuno Y., Shimizu N. Mutations in the parkin gene cause autosomal recessive juvenile parkinsonism. Nature. 1998 Apr 9;392(6676):605–608. doi: 10.1038/33416. [DOI] [PubMed] [Google Scholar]
  15. Klement I. A., Skinner P. J., Kaytor M. D., Yi H., Hersch S. M., Clark H. B., Zoghbi H. Y., Orr H. T. Ataxin-1 nuclear localization and aggregation: role in polyglutamine-induced disease in SCA1 transgenic mice. Cell. 1998 Oct 2;95(1):41–53. doi: 10.1016/s0092-8674(00)81781-x. [DOI] [PubMed] [Google Scholar]
  16. Knight S. A., Kim R., Pain D., Dancis A. The yeast connection to Friedreich ataxia. Am J Hum Genet. 1999 Feb;64(2):365–371. doi: 10.1086/302270. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Leroy E., Boyer R., Auburger G., Leube B., Ulm G., Mezey E., Harta G., Brownstein M. J., Jonnalagada S., Chernova T. The ubiquitin pathway in Parkinson's disease. Nature. 1998 Oct 1;395(6701):451–452. doi: 10.1038/26652. [DOI] [PubMed] [Google Scholar]
  18. Li M., Miwa S., Kobayashi Y., Merry D. E., Yamamoto M., Tanaka F., Doyu M., Hashizume Y., Fischbeck K. H., Sobue G. Nuclear inclusions of the androgen receptor protein in spinal and bulbar muscular atrophy. Ann Neurol. 1998 Aug;44(2):249–254. doi: 10.1002/ana.410440216. [DOI] [PubMed] [Google Scholar]
  19. Lin C. L., Bristol L. A., Jin L., Dykes-Hoberg M., Crawford T., Clawson L., Rothstein J. D. Aberrant RNA processing in a neurodegenerative disease: the cause for absent EAAT2, a glutamate transporter, in amyotrophic lateral sclerosis. Neuron. 1998 Mar;20(3):589–602. doi: 10.1016/s0896-6273(00)80997-6. [DOI] [PubMed] [Google Scholar]
  20. Martindale D., Hackam A., Wieczorek A., Ellerby L., Wellington C., McCutcheon K., Singaraja R., Kazemi-Esfarjani P., Devon R., Kim S. U. Length of huntingtin and its polyglutamine tract influences localization and frequency of intracellular aggregates. Nat Genet. 1998 Feb;18(2):150–154. doi: 10.1038/ng0298-150. [DOI] [PubMed] [Google Scholar]
  21. Matilla A., Koshy B. T., Cummings C. J., Isobe T., Orr H. T., Zoghbi H. Y. The cerebellar leucine-rich acidic nuclear protein interacts with ataxin-1. Nature. 1997 Oct 30;389(6654):974–978. doi: 10.1038/40159. [DOI] [PubMed] [Google Scholar]
  22. Merry D. E., Kobayashi Y., Bailey C. K., Taye A. A., Fischbeck K. H. Cleavage, aggregation and toxicity of the expanded androgen receptor in spinal and bulbar muscular atrophy. Hum Mol Genet. 1998 Apr;7(4):693–701. doi: 10.1093/hmg/7.4.693. [DOI] [PubMed] [Google Scholar]
  23. Paulson H. L., Perez M. K., Trottier Y., Trojanowski J. Q., Subramony S. H., Das S. S., Vig P., Mandel J. L., Fischbeck K. H., Pittman R. N. Intranuclear inclusions of expanded polyglutamine protein in spinocerebellar ataxia type 3. Neuron. 1997 Aug;19(2):333–344. doi: 10.1016/s0896-6273(00)80943-5. [DOI] [PubMed] [Google Scholar]
  24. Pellizzoni L., Kataoka N., Charroux B., Dreyfuss G. A novel function for SMN, the spinal muscular atrophy disease gene product, in pre-mRNA splicing. Cell. 1998 Nov 25;95(5):615–624. doi: 10.1016/s0092-8674(00)81632-3. [DOI] [PubMed] [Google Scholar]
  25. Perez M. K., Paulson H. L., Pendse S. J., Saionz S. J., Bonini N. M., Pittman R. N. Recruitment and the role of nuclear localization in polyglutamine-mediated aggregation. J Cell Biol. 1998 Dec 14;143(6):1457–1470. doi: 10.1083/jcb.143.6.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Perutz M. F., Johnson T., Suzuki M., Finch J. T. Glutamine repeats as polar zippers: their possible role in inherited neurodegenerative diseases. Proc Natl Acad Sci U S A. 1994 Jun 7;91(12):5355–5358. doi: 10.1073/pnas.91.12.5355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Price D. L., Sisodia S. S., Borchelt D. R. Genetic neurodegenerative diseases: the human illness and transgenic models. Science. 1998 Nov 6;282(5391):1079–1083. doi: 10.1126/science.282.5391.1079. [DOI] [PubMed] [Google Scholar]
  28. Reddy P. H., Williams M., Charles V., Garrett L., Pike-Buchanan L., Whetsell W. O., Jr, Miller G., Tagle D. A. Behavioural abnormalities and selective neuronal loss in HD transgenic mice expressing mutated full-length HD cDNA. Nat Genet. 1998 Oct;20(2):198–202. doi: 10.1038/2510. [DOI] [PubMed] [Google Scholar]
  29. Saudou F., Finkbeiner S., Devys D., Greenberg M. E. Huntingtin acts in the nucleus to induce apoptosis but death does not correlate with the formation of intranuclear inclusions. Cell. 1998 Oct 2;95(1):55–66. doi: 10.1016/s0092-8674(00)81782-1. [DOI] [PubMed] [Google Scholar]
  30. Scherzinger E., Lurz R., Turmaine M., Mangiarini L., Hollenbach B., Hasenbank R., Bates G. P., Davies S. W., Lehrach H., Wanker E. E. Huntingtin-encoded polyglutamine expansions form amyloid-like protein aggregates in vitro and in vivo. Cell. 1997 Aug 8;90(3):549–558. doi: 10.1016/s0092-8674(00)80514-0. [DOI] [PubMed] [Google Scholar]
  31. Sittler A., Wälter S., Wedemeyer N., Hasenbank R., Scherzinger E., Eickhoff H., Bates G. P., Lehrach H., Wanker E. E. SH3GL3 associates with the Huntingtin exon 1 protein and promotes the formation of polygln-containing protein aggregates. Mol Cell. 1998 Oct;2(4):427–436. doi: 10.1016/s1097-2765(00)80142-2. [DOI] [PubMed] [Google Scholar]
  32. Trottier Y., Lutz Y., Stevanin G., Imbert G., Devys D., Cancel G., Saudou F., Weber C., David G., Tora L. Polyglutamine expansion as a pathological epitope in Huntington's disease and four dominant cerebellar ataxias. Nature. 1995 Nov 23;378(6555):403–406. doi: 10.1038/378403a0. [DOI] [PubMed] [Google Scholar]
  33. Warrick J. M., Paulson H. L., Gray-Board G. L., Bui Q. T., Fischbeck K. H., Pittman R. N., Bonini N. M. Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila. Cell. 1998 Jun 12;93(6):939–949. doi: 10.1016/s0092-8674(00)81200-3. [DOI] [PubMed] [Google Scholar]
  34. Wellington C. L., Ellerby L. M., Hackam A. S., Margolis R. L., Trifiro M. A., Singaraja R., McCutcheon K., Salvesen G. S., Propp S. S., Bromm M. Caspase cleavage of gene products associated with triplet expansion disorders generates truncated fragments containing the polyglutamine tract. J Biol Chem. 1998 Apr 10;273(15):9158–9167. doi: 10.1074/jbc.273.15.9158. [DOI] [PubMed] [Google Scholar]

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