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Title: | Deranged calcium signaling and neurodegeneration in spinocerebellar ataxia type 3 |
Authors: | Chen, X Tang, TS Tu, H Nelson, O Pook, M Hammer, R Nukina, N Bezprozvanny, I |
Keywords: | SCA3;MJD |
Issue Date: | 2008 |
Publisher: | Society for Neuroscience |
Citation: | The Journal of Neuroscience. 28(48): 12713-12724 |
Abstract: | Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease (MJD), is an autosomal-dominant neurodegenerative disorder caused by a polyglutamine expansion in ataxin-3 (SCA3, MJD1) protein. In biochemical experiments we demonstrate that mutant SCA3exp specifically associated with the type 1 inositol 1,4,5-trisphosphate receptor (InsP3R1), an intracellular calcium (Ca2+) release channel. In electrophysiological and Ca2+ imaging experiments we show that InsP3R1 are sensitized to activation by InsP3 in the presence of mutant SCA3exp. We found that feeding SCA3-YAC-84Q transgenic mice with dantrolene, a clinically relevant stabilizer of intracellular Ca2+ signaling, improved their motor performance and prevented neuronal cells loss in pontine nuclei and substantia nigra regions. Our results indicate that deranged Ca2+ signaling may play an important role in SCA3 pathology and that Ca2+ signaling stabilizers such as dantrolene may be considered as potential therapeutic drugs for treatment of SCA3 patients. |
URI: | http://bura.brunel.ac.uk/handle/2438/3132 |
DOI: | http://dx.doi.org/10.1523/JNEUROSCI.3909-08.2008 |
Appears in Collections: | Community Health and Public Health Dept of Life Sciences Research Papers |
Files in This Item:
File | Description | Size | Format | |
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Chen submitted.pdf | 551.98 kB | Adobe PDF | View/Open |
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