RNA-mediated neurodegeneration in repeat expansion disorders
dc.contributor.author | Todd, Peter K. | en_US |
dc.contributor.author | Paulson, Henry L. | en_US |
dc.date.accessioned | 2010-04-14T20:04:56Z | |
dc.date.available | 2011-03-01T16:26:47Z | en_US |
dc.date.issued | 2010-03 | en_US |
dc.identifier.citation | Todd, Peter K.; Paulson, Henry L. (2010). "RNA-mediated neurodegeneration in repeat expansion disorders." Annals of Neurology 67(3): 291-300. <http://hdl.handle.net/2027.42/69199> | en_US |
dc.identifier.issn | 0364-5134 | en_US |
dc.identifier.issn | 1531-8249 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/69199 | |
dc.description.abstract | Most neurodegenerative disorders are thought to result primarily from the accumulation of misfolded proteins, which interfere with protein homeostasis in neurons. For a subset of diseases, however, noncoding regions of RNAs assume a primary toxic gain-of-function, leading to degeneration in many tissues, including the nervous system. Here we review a series of proposed mechanisms by which noncoding repeat expansions give rise to nervous system degeneration and dysfunction. These mechanisms include transcriptional alterations and the generation of antisense transcripts, sequestration of mRNA-associated protein complexes that lead to aberrant mRNA splicing and processing, and alterations in cellular processes, including activation of abnormal signaling cascades and failure of protein quality control pathways. We place these potential mechanisms in the context of known RNA-mediated disorders, including the myotonic dystrophies and fragile X tremor ataxia syndrome, and discuss recent results suggesting that mRNA toxicity may also play a role in some presumably protein-mediated neurodegenerative disorders. Lastly, we comment on recent progress in therapeutic development for these RNA-dominant diseases. ANN NEUROL 2010;67:291–300 | en_US |
dc.format.extent | 301158 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Wiley Subscription Services, Inc., A Wiley Company | en_US |
dc.subject.other | Life and Medical Sciences | en_US |
dc.subject.other | Neuroscience, Neurology, and Psychiatry | en_US |
dc.title | RNA-mediated neurodegeneration in repeat expansion disorders | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Psychiatry | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Department of Neurology, University of Michigan, Ann Arbor, MI ; 109 Zina Pitcher Place, 4188 BSRB, Ann Arbor, MI 48109-2200 | en_US |
dc.contributor.affiliationum | Department of Neurology, University of Michigan, Ann Arbor, MI | en_US |
dc.identifier.pmid | 20373340 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/69199/1/21948_ftp.pdf | |
dc.identifier.doi | 10.1002/ana.21948 | en_US |
dc.identifier.source | Annals of Neurology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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