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

An international research team has provided the first conclusive evidence that neurodevelopmental disorders such as mental retardation and neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and ataxias can be caused, at least in part, by specific gene defects that interfere with the electrical impulses of rapid-firing brain nerve cells called bursting neurons.

The implicated gene, KCNC3, and two mutations are described in the journal Nature Genetics, published online Feb. 26, 2006. Until now, theories on degenerative cell death have centered on defective proteins and/or their accumulation and aggregation in the brain.

"The neurodegeneration field has been dominated by the hypothesis of misfolded proteins and their aggregation, but the identification of KCNC3 mutations and their functional characterization represent a novel avenue for understanding cell death," said Stefan M. Pulst, M.D., director of the Division of Neurology at Cedars-Sinai Medical Center, holder of the Carmen and Louis Warschaw Chair in Neurology, and principal investigator of this study.

KCNC3 forms a potassium channel, part of a biochemical mechanism that regulates the electrical impulses of bursting neurons. Although potassium channel mutations have previously been linked to episodic disorders such as seizures, this is the first time they have been identified as causative factors ?and potentially therapeutic targets ?in neurodegenerative diseases.

"Very recent neurophysiological studies of bursting neurons have led to speculation that voltage-gated potassium channels could be involved in human neurodegenerative disease, but proof has been lacking," Pulst said. "This is the first time neurodegeneration has been directly linked to potassium channel mutations."

In the Nature Genetics article, the researchers describe their analysis of two ataxia-causing mutations of the KCNC3 gene ?one present in a Filipino family and one in a French 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 e.


'"/>

Source:Cedars-Sinai Medical Center


Related biology news :

1. Novel Asthma Study Shows Multiple Genetic Input Required; Single-gene Solution Shot Down
2. Emory Study Tests Bone Marrow Stem Cells to Improve Circulation in Legs
3. UCLA Study Shows One-Third of Drug Ads in Medical Journals Do Not Contain References Supporting Medical Claims
4. Study Demonstrates Gene Expression Microarrays are Comparable and Reproducible
5. Study Links Ebola Outbreaks To Animal Carcasses
6. Breakthrough Microarray-based Technology for the Study of Cancer
7. NYU Study Reveals How Brains Immune System Fights Viral Encephalitis
8. Study finds more than one-third of human genome regulated by RNA
9. Leukemia Drug Breakthrough Study In New England Journal Of Medicine
10. Study identifies predictors of HIV drug resistance in patients beginning triple therapy
11. New Study from Affymetrix Laboratories Points to Changing View of How Genome Works
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/15/2016)... , April 15, 2016 ... "Global Gait Biometrics Market 2016-2020,"  report to their ... ) , ,The global gait biometrics market ... 13.98% during the period 2016-2020. Gait ... which can be used to compute factors that ...
(Date:4/13/2016)... CHICAGO , April 13, 2016  IMPOWER physicians ... are setting a new clinical standard in telehealth ... By leveraging the higi platform, IMPOWER patients can ... weight, pulse and body mass index, and, when they ... quick and convenient visit to a local retail location ...
(Date:3/31/2016)... 31, 2016  Genomics firm Nabsys has completed a ... Barrett Bready , M.D., who returned to the company ... technical leadership team, including Chief Technology Officer, John ... Steve Nurnberg and Vice President of Software and Informatics, ... Dr. Bready served as CEO of Nabsys ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... Hill, N.C. (PRWEB) , ... June 27, 2016 ... ... U.S. commercial operations for Amgen, will join the faculty of the University ... serve as adjunct professor of strategy and entrepreneurship at UNC Kenan-Flagler, with a ...
(Date:6/27/2016)... --  Ginkgo Bioworks , a leading organism design ... awarded as one of the World Economic Forum,s ... innovative companies. Ginkgo Bioworks is engineering biology to ... in the nutrition, health and consumer goods sectors. ... including Fortune 500 companies to design microbes for ...
(Date:6/24/2016)... 2016 Epic Sciences unveiled a liquid ... to PARP inhibitors by targeting homologous recombination deficiency ... new test has already been incorporated into numerous ... types. Over 230 clinical trials are ... including PARP, ATM, ATR, DNA-PK and WEE-1. Drugs ...
(Date:6/24/2016)... ... June 24, 2016 , ... Researchers at the Universita Politecnica delle ... people with peritoneal or pleural mesothelioma. Their findings are the subject of a new ... , Diagnostic biomarkers are signposts in the blood, lung fluid or tissue of mesothelioma ...
Breaking Biology Technology: