Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Scientists identify fundamental brain defect, probable drug target in fragile X syndrome

18.09.2007
Scientists have discovered how the gene mutation responsible for fragile X syndrome--the most common inherited form of mental retardation--alters the way brain cells communicate. In neurons cultured from laboratory rats, the scientists also were able to reverse the effects of the mutation using a drug targeted to the specific site in an upstream pathway of the defect. The finding could lead to the development of human therapies for this previously untreatable condition.

The research was led by Stephen T. Warren, PhD, Timmie professor and chair of human genetics in Emory University School of Medicine, and Gary J. Bassell, PhD, Emory professor of cell biology. It will be reported in the Proceedings of the National Academy of Sciences (PNAS) the week of Sept. 17. Lead author is Emory genetics postdoctoral fellow Mika Nakamoto.

"We have now explained the fundamental defect in the brain in fragile X syndrome and, most importantly, found that we can correct this problem in the laboratory," says Dr. Warren. "This is quite exciting, progressing from the identification of the gene in 1991 to now believing we will be able to treat a previously untreatable condition. Our next steps will be to continue screening and identifying the best drugs to try and correct the deficiencies that result from fragile X syndrome."

Fragile X syndrome is caused by a mutation in the FMR1 gene on the X chromosome. A region of the mutated FMR1 gene repeats a trinucleotide sequence of DNA bases--CGG--between 200 and 1,000 times, rather than the normal 6 to 55 repeats in normal individuals. The abnormal trinucleotide repeats cause the absence of the FMR protein normally produced by the gene.

... more about:
»AMPAR »Drug »FMRP »Syndrome »Target »discovered »mGluR5 »receptor

Dr. Warren and his colleagues led an international team that discovered the FMR1 gene in 1991. They later characterized the FMR protein (FMRP) and developed diagnostic tests for fragile X syndrome. Ever since, their research has focused on identifying the specific consequences of FMRP deficiency in the brain and finding targets for drug therapy.

Previously, Dr. Warren, working with scientists at Brown University, discovered that the absence of FMRP in the mouse model of fragile X syndrome leads to an abnormality in synaptic strength, or the degree by which neurons communicate, that suggested an abnormality of AMPAR receptors on the surface of neurons. These receptors are necessary for neurons to connect with each other at synapses, allowing the communication that leads to learning and memory. Drs. Warren and Bassell discovered that in fragile X syndrome, AMPAR receptors move in and out of the surface neuronal cells more frequently and destabilize the synaptic connections. The Emory scientists and others believe this is the ultimate defect in fragile X syndrome.

Using cultured neurons in the laboratory, manipulated to model fragile X syndrome, the Emory scientists were able to target the mGluR5 receptor with an mGluR5 antagonist--MPEP. Since the mGluR5 receptor is upstream of FMRP and has an opposing influence over the neuron, tempering mGluR5 stimulation should normalize the consequence of the loss of FMRP. Indeed, the Emory scientists found the targeted MPEP therapy rescued the abnormal AMPAR receptor movement on the surface of the FMRP-deficient neurons.

"By adding a drug that antagonizes the mGluR5 receptor and signal, we were able to normalize the AMPAR receptor trafficking, and presumably allow the neurons to make appropriate synaptic connections," Dr. Warren says. "This gives us great hope that we will be able to develop treatments for patients with fragile X syndrome."

Holly Korschun | EurekAlert!
Further information:
http://www.emory.edu

Further reports about: AMPAR Drug FMRP Syndrome Target discovered mGluR5 receptor

More articles from Life Sciences:

nachricht Two Group A Streptococcus genes linked to 'flesh-eating' bacterial infections
25.09.2017 | University of Maryland

nachricht Rainbow colors reveal cell history: Uncovering β-cell heterogeneity
22.09.2017 | DFG-Forschungszentrum für Regenerative Therapien TU Dresden

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: LaserTAB: More efficient and precise contacts thanks to human-robot collaboration

At the productronica trade fair in Munich this November, the Fraunhofer Institute for Laser Technology ILT will be presenting Laser-Based Tape-Automated Bonding, LaserTAB for short. The experts from Aachen will be demonstrating how new battery cells and power electronics can be micro-welded more efficiently and precisely than ever before thanks to new optics and robot support.

Fraunhofer ILT from Aachen relies on a clever combination of robotics and a laser scanner with new optics as well as process monitoring, which it has developed...

Im Focus: The pyrenoid is a carbon-fixing liquid droplet

Plants and algae use the enzyme Rubisco to fix carbon dioxide, removing it from the atmosphere and converting it into biomass. Algae have figured out a way to increase the efficiency of carbon fixation. They gather most of their Rubisco into a ball-shaped microcompartment called the pyrenoid, which they flood with a high local concentration of carbon dioxide. A team of scientists at Princeton University, the Carnegie Institution for Science, Stanford University and the Max Plank Institute of Biochemistry have unravelled the mysteries of how the pyrenoid is assembled. These insights can help to engineer crops that remove more carbon dioxide from the atmosphere while producing more food.

A warming planet

Im Focus: Highly precise wiring in the Cerebral Cortex

Our brains house extremely complex neuronal circuits, whose detailed structures are still largely unknown. This is especially true for the so-called cerebral cortex of mammals, where among other things vision, thoughts or spatial orientation are being computed. Here the rules by which nerve cells are connected to each other are only partly understood. A team of scientists around Moritz Helmstaedter at the Frankfiurt Max Planck Institute for Brain Research and Helene Schmidt (Humboldt University in Berlin) have now discovered a surprisingly precise nerve cell connectivity pattern in the part of the cerebral cortex that is responsible for orienting the individual animal or human in space.

The researchers report online in Nature (Schmidt et al., 2017. Axonal synapse sorting in medial entorhinal cortex, DOI: 10.1038/nature24005) that synapses in...

Im Focus: Tiny lasers from a gallery of whispers

New technique promises tunable laser devices

Whispering gallery mode (WGM) resonators are used to make tiny micro-lasers, sensors, switches, routers and other devices. These tiny structures rely on a...

Im Focus: Ultrafast snapshots of relaxing electrons in solids

Using ultrafast flashes of laser and x-ray radiation, scientists at the Max Planck Institute of Quantum Optics (Garching, Germany) took snapshots of the briefest electron motion inside a solid material to date. The electron motion lasted only 750 billionths of the billionth of a second before it fainted, setting a new record of human capability to capture ultrafast processes inside solids!

When x-rays shine onto solid materials or large molecules, an electron is pushed away from its original place near the nucleus of the atom, leaving a hole...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

“Lasers in Composites Symposium” in Aachen – from Science to Application

19.09.2017 | Event News

I-ESA 2018 – Call for Papers

12.09.2017 | Event News

EMBO at Basel Life, a new conference on current and emerging life science research

06.09.2017 | Event News

 
Latest News

Fraunhofer ISE Pushes World Record for Multicrystalline Silicon Solar Cells to 22.3 Percent

25.09.2017 | Power and Electrical Engineering

Usher syndrome: Gene therapy restores hearing and balance

25.09.2017 | Health and Medicine

An international team of physicists a coherent amplification effect in laser excited dielectrics

25.09.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>