Navigation Links
UI study finds potential genetic link between epilepsy and neurodegenerative disorders
Date:7/22/2014

A recent scientific discovery showed that mutations in prickle genes cause epilepsy, which in humans is a brain disorder characterized by repeated seizures over time. However, the mechanism responsible for generating prickle-associated seizures was unknown.

A new University of Iowa study, published online July 14 in the Proceedings of the National Academy of Sciences, reveals a novel pathway in the pathophysiology of epilepsy. UI researchers have identified the basic cellular mechanism that goes awry in prickle mutant flies, leading to the epilepsy-like seizures.

"This is to our knowledge the first direct genetic evidence demonstrating that mutations in the fly version of a known human epilepsy gene produce seizures through altered vesicle transport," says John Manak, senior author and associate professor of biology in the College of Liberal Arts and Sciences and pediatrics in the Carver College of Medicine.

Seizure suppression in flies

A neuron has an axon (nerve fiber) that projects from the cell body to different neurons, muscles, and glands. Information is transmitted along the axon to help a neuron function properly.

Manak and his fellow researchers show that seizure-prone prickle mutant flies have behavioral defects (such as uncoordinated gait) and electrophysiological defects (problems in the electrical properties of biological cells) similar to other fly mutants used to study seizures. The researchers also show that altering the balance of two forms of the prickle gene disrupts neural information flow and causes epilepsy.

Further, they demonstrate that reducing either of two motor proteins responsible for directional movement of vesicles (small organelles within a cell that contain biologically important molecules) along tracks of structural proteins in axons can suppress the seizures.

"The reduction of either of two motor proteins, called Kinesins, fully suppressed the seizures in the prickle mutant flies," says Manak, faculty member in the Interdisciplinary Graduate Programs in Genetics, Molecular and Cellular Biology, and Health Informatics. "We were able to use two independent assays to show that we could suppress the seizures, effectively 'curing' the flies of their epileptic behaviors."

Genetic link between epilepsy and Alzheimer's

This new epilepsy pathway was previously shown to be involved in neurodegenerative diseases, including Alzheimer's and Parkinson's.

Manak and his colleagues note that two Alzheimer's-associated proteins, amyloid precursor protein and presenilin, are components of the same vesicle, and mutations in the genes encoding these proteins in flies affect vesicle transport in ways that are strikingly similar to how transport is impacted in prickle mutants.

"We are particularly excited because we may have stumbled upon one of the key genetic links between epilepsy and Alzheimer's, since both disorders are converging on the same pathway," Manak says. "This is not such a crazy idea. In fact, Dr. Jeff Noebels, a leading epilepsy researcher, has presented compelling evidence suggesting a link between these disorders. Indeed, patients with inherited forms of Alzheimer's disease also present with epilepsy, and this has been documented in a number of published studies."

Manak adds, "If this connection is real, then drugs that have been developed to treat neurodegenerative disorders could potentially be screened for anti-seizure properties, and vice versa."

Manak's future research will involve treating seizure-prone flies with such drugs to see if he can suppress their seizures.


'/>"/>

Contact: Gary Galluzzo
gary-galluzzo@uiowa.edu
319-384-0009
University of Iowa
Source:Eurekalert

Related biology news :

1. New study reveals vulnerability of sharks as collateral damage in commercial fishing
2. Vanderbilt study shows therapeutic bacteria prevent obesity in mice
3. Study compares cost-effectiveness of weight-loss programs and drugs
4. Natural-terrain schoolyards reduce childrens stress, says Colorado University-Boulder study
5. Meerkats sinister side is secret to their success, study shows
6. Studying estrogens made by the brain may offer new insights in learning and memory
7. Study provides insights into birds migration routes
8. LEDs shine in bedding plant production study
9. Large twin study suggests that language delay due more to nature than nurture
10. Size and age of plants impact their productivity more than climate, study shows
11. Economic development not the only influence on personal car use, study finds
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:6/27/2016)... June 27, 2016 Research and Markets has ... 2016-2020" report to their offering. ... America to grow at a CAGR of 12.28% during ... based on an in-depth market analysis with inputs from industry experts. ... the coming years. The report also includes a discussion of the ...
(Date:6/22/2016)... , June 22, 2016  The American College of Medical ... Show Executive Magazine as one of the fastest-growing trade ... 25-27 at the Bellagio in Las Vegas ... highest percentage of growth in each of the following categories: ... companies and number of attendees. The 2015 ACMG Annual Meeting ...
(Date:6/22/2016)... 22, 2016   Acuant , the ... solutions, has partnered with RightCrowd ® ... Visitor Management, Self-Service Kiosks and Continuous Workforce ... add functional enhancements to existing physical access ... venues with an automated ID verification and ...
Breaking Biology News(10 mins):
(Date:6/23/2016)... 23, 2016   EpiBiome , a precision microbiome ... in debt financing from Silicon Valley Bank (SVB). The ... to advance its drug development efforts, as well as ... "SVB has been an incredible strategic partner to ... traditional bank would provide," said Dr. Aeron Tynes ...
(Date:6/23/2016)... Apellis Pharmaceuticals, Inc. today announced positive ... its complement C3 inhibitor, APL-2. The trials were ... studies designed to assess the safety, tolerability, pharmacokinetics ... healthy adult volunteers. Forty subjects were ... dose (ranging from 45 to 1,440mg) or repeated ...
(Date:6/23/2016)... ... June 23, 2016 , ... ... at the Pennsylvania Convention Center and will showcase its product’s latest features from ... also be presenting a scientific poster on Disrupting Clinical Trials in The Cloud ...
(Date:6/23/2016)... India , June 23, 2016 ... media market research report to its pharmaceuticals section ... profiles, product details and much more. ... spread across 151 pages, profiling 15 companies and ... available at http://www.reportsnreports.com/reports/601420-global-cell-culture-media-industry-2016-market-research-report.html . ...
Breaking Biology Technology: