'Deranged calcium signaling' contributes to neurological disorder, UT Southwestern resear...(/p Such abnormal calcium release is t...)
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Such abnormal calcium release is toxic to cells and results in impaired motor function, said Dr. Ilya Bezprozvanny, professor of physiology at UT Southwestern and senior author of the study. "We're generalizing the idea of calcium toxicity for this group of diseases, which are called polyglutamine expansion disorders," he said.
The researchers also studied mice that had been genetically engineered to overexpress the human ataxin-3 protein containing excessive glutamine repeats. The mutant mice performed poorly on tests of motor coordination compared with normal mice and displayed age-dependent neuronal loss in the same brain regions that are affected in SCA3 patients.
To test whether blocking calcium release would alleviate symptoms in the mice, the researchers treated them for a year with dantrolene, a drug that blocks excessive calcium release from the ER in skeletal muscle cells. Dantrolene is approved for use in humans as a one-time emergency treatment for a reaction to anesthesia.
Treatment with dantrolene improved the coordination of the mutant mice and slowed brain atrophy.
Dantrolene is not suitable for long-term use in humans, however, because of side effects that can potentially harm the liver and the heart and cause neurological problems, said Dr. Bezprozvanny.
"The take-home message is not so much that dantrolene is the solution for treating SCA3, but that this shows a direction for research into a better drug to block similar targets with fewer side effects," Dr. Bezprozvanny said.
The researchers now are studying whether blocking calcium release from the endoplasmic reticulum also can improve function in mouse models of Huntington's and other neurodegenerative diseases such as spinocerebellar ataxia type 2 and Alzheimer's disease.
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| Contact: Aline McKenzie aline.mckenzie@utsouthwestern.edu 214-648-3404 UT Southwestern Medical Center Source:Eurekalert |
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 'Deranged calcium signaling' contributes to neurological disorder, UT Southwestern researchers find |
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