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Study ties 'new' cell-death mechanism to developmental and degenerative brain disorders

family. Although both mutations affect the firing of cerebellar neurons, they impact them in different ways and apparently lead to different disease manifestations.

The Filipino family's ataxia is an adult-onset type with prominent motor coordination symptoms and cerebellar atrophy. The French family's ataxia is a childhood-onset type, with mental retardation and seizures in some individuals. With mental retardation as one of the consequences, the KCNC3 potassium channel mutations are linked to neurodevelopmental as well as neurodegenerative disorders.

Spinocerebellar ataxias (SCA) include a number of hereditary neurological disorders, some of which emerge in childhood and others in adulthood, affecting one in 17,000 people. Ataxias affect coordination and many basic functions such as walking and speaking. They also may lead to eye movement abnormalities, cognitive decline, epilepsy and other significant deficits.

Twenty-seven specific locations on human chromosomes have been identified for involvement in the development of ataxias, and 10 causative genes or mutations have been determined. The gene and mutations in this study affect the SCA13 gene.

Ataxias are characterized by degeneration of nerve cells in the cerebellum, while the cell death of Alzheimer's disease takes place in the hippocampus of the temporal lobe and that of Parkinson's disease occurs in the substantia nigra of the brain stem.

Pulst said the new findings on neurodegeneration do not necessarily supersede the prevailing hypothesis of defective proteins. In fact, the two may be linked.

"It could be that the behavior of the nerve cell is altered, making it more susceptible to the onslaught of misfolded proteins, and it could be that misfolded proteins interfere in channel functions," said Pulst, who led a team of scientists from Cedars-Sinai Medical Center, the University of California, Los Angeles, the Mayo Clinic and the Pasteur Institute in Franc
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Source:Cedars-Sinai Medical Center


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