Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila
- PMID: 9635424
- DOI: 10.1016/s0092-8674(00)81200-3
Expanded polyglutamine protein forms nuclear inclusions and causes neural degeneration in Drosophila
Abstract
Spinocerebellar ataxia type 3 (SCA3/MJD) is one of at least eight human neurodegenerative diseases caused by glutamine-repeat expansion. We have recreated glutamine-repeat disease in Drosophila using a segment of the SCA3/MJD protein. _targeted expression of the protein with an expanded polyglutamine repeat led to nuclear inclusion (NI) formation and late-onset cell degeneration. Differential sensitivity to the mutant transgene was observed among different cell types, with neurons being particularly susceptible; NI formation alone was not sufficient for degeneration. The viral antiapoptotic gene P35 mitigated polyglutamine-induced degeneration in vivo. Our results demonstrate that cellular mechanisms of human glutamine-repeat disease are conserved in invertebrates. This fly model will aid in identifying additional factors that modulate neurodegeneration.
Similar articles
-
A genetic model for human polyglutamine-repeat disease in Drosophila melanogaster.Philos Trans R Soc Lond B Biol Sci. 1999 Jun 29;354(1386):1057-60. doi: 10.1098/rstb.1999.0458. Philos Trans R Soc Lond B Biol Sci. 1999. PMID: 10434305 Free PMC article.
-
Expression of expanded polyglutamine protein induces behavioral changes in Drosophila (polyglutamine-induced changes in Drosophila).Cell Mol Neurobiol. 2004 Feb;24(1):109-22. doi: 10.1023/b:cemn.0000012716.14075.25. Cell Mol Neurobiol. 2004. PMID: 15049515
-
Recruitment and the role of nuclear localization in polyglutamine-mediated aggregation.J Cell Biol. 1998 Dec 14;143(6):1457-70. doi: 10.1083/jcb.143.6.1457. J Cell Biol. 1998. PMID: 9852144 Free PMC article.
-
Mouse models of Machado-Joseph disease and other polyglutamine spinocerebellar ataxias.NeuroRx. 2005 Jul;2(3):480-3. doi: 10.1602/neurorx.2.3.480. NeuroRx. 2005. PMID: 16389311 Free PMC article. Review.
-
Machado-Joseph disease/spinocerebellar ataxia type 3.Handb Clin Neurol. 2012;103:437-49. doi: 10.1016/B978-0-444-51892-7.00027-9. Handb Clin Neurol. 2012. PMID: 21827905 Free PMC article. Review.
Cited by
-
Therapeutic prospects for spinocerebellar ataxia type 2 and 3.Drugs Future. 2009 Dec;34(12):10.1358/dof.2009.034.12.1443434. doi: 10.1358/dof.2009.034.12.1443434. Drugs Future. 2009. PMID: 26023252 Free PMC article.
-
Effect of αB-crystallin on protein aggregation in Drosophila.J Biomed Biotechnol. 2012;2012:252049. doi: 10.1155/2012/252049. Epub 2012 Mar 7. J Biomed Biotechnol. 2012. PMID: 22505806 Free PMC article.
-
Sodium valproate alleviates neurodegeneration in SCA3/MJD via suppressing apoptosis and rescuing the hypoacetylation levels of histone H3 and H4.PLoS One. 2013;8(1):e54792. doi: 10.1371/journal.pone.0054792. Epub 2013 Jan 28. PLoS One. 2013. PMID: 23382971 Free PMC article.
-
Boat, an AXH domain protein, suppresses the cytotoxicity of mutant ataxin-1.EMBO J. 2005 Sep 21;24(18):3339-51. doi: 10.1038/sj.emboj.7600785. Epub 2005 Aug 25. EMBO J. 2005. PMID: 16121196 Free PMC article.
-
Transcription profiling in Drosophila eyes that overexpress the human glaucoma-associated trabecular meshwork-inducible glucocorticoid response protein/myocilin (TIGR/MYOC).Genetics. 2003 Feb;163(2):637-45. doi: 10.1093/genetics/163.2.637. Genetics. 2003. PMID: 12618402 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Research Materials
