Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A Fly Mutation Suggests a New Route for Tackling ALS

09.04.2013
A team of researchers, led by Marc Freeman, PhD, an early career scientist with the Howard Hughes Medical Institute and associate professor of neurobiology at the University of Massachusetts Medical School have discovered a gene in the fruit fly Drosophila melanogaster that, when mutant, blocks the self-destruction of damaged axons, which could hold clues to treating motor neuron diseases, such as amyotrophic lateral sclerosis (ALS).

A neuron has a very distinctive form – a bush of dendrites that receive signals, an incredibly long axon, which is like a long tail, and “a little dot” between them that is the cell body, housing the genetic headquarters. Every part of the neuron is required for it to transmit messages.

“If anything breaks along any part of the neuron, the cell unplugs from the circuit and no longer functions,” explained Dr. Freeman, who presented this research at the Genetics Society of America’s 54th Annual Drosophila Research Conference in Washington, D.C.

Once the long tail-like axon is damaged, it shrivels away, basically self-destructing, and resulting in neurons that no longer operate. This catastrophic damage can happen in several ways: from inflammation, a neurodegenerative disease, a metabolic disorder such as diabetes, toxin exposure, or tumor growth. Such axon loss is thought to be a primary factor that leads to functional loss in patients with neurological disorders – it is equivalent to going into an electrical circuit and randomly cutting wires.

The study of axon destruction in response to damage goes back to British neurophysiologist Augustus Waller, who in 1850 described how an axon separated from the cell body and cut off from its nutrient supply breaks apart and is dismantled by scavenger cells. “The idea that this process, called Wallerian degeneration, was a passive wasting away of the axon held for 150 years,” Dr. Freeman said.

Then in the late 1980s, researchers discovered a mutation in the mouse, called Wlds, which enables a damaged axon to survive for weeks after injury. “That fundamentally changed how we think about an axon. Under certain circumstances, axons can survive for a much longer time than we have given them credit for,” Dr. Freeman explained.

Freeman’s laboratory speculated that if axon self-destruction is an active process, then there should be genes in the fly genome whose normal function is to destroy cut axons. They decided if they could break those genes responsible for axon destruction, then the axons shouldn’t fall apart. To identify those genes, they performed a labor-intensive screen, randomly breaking genes in the fly genome and looking for those that when broken blocked axon destruction after injury.

This approach led to the identification of one gene, called dSarm, whose normal function is to promote the destruction of the axon after injury. “We got beautiful protection of axons when we knocked out this molecule,” Dr. Freeman said. Mice and humans have forms of this gene too, and Freeman and colleagues have shown its functions in a similar way in mice. The preservation of these signaling mechanisms from flies to humans is a sign of evolutionary retention and argues for its importance.

To get closer to applying the axon death gene to the study of disease, the researchers crossed the mouse version of the Sarm mutation into a mouse model that has a type of familial ALS, which is also in humans. Although the mice still lost weight and had difficulty with a mobility test, they lived about 10 days longer than their brethren without the Sarm mutation, and at least half of their motor neurons remained intact. “Since not all the motor neurons are needed,” Dr. Freeman said, “even with a 50 percent reduction a patient could feel very close to normal. It would be life-changing for the patient, so it’s a step in the right direction.”

“We used Wallerian degeneration as a model for axon degeneration. We’ve identified a signal pathway whose normal function is to promote axon destruction after injury, and hope to build on this research to better understand the role of axon death in neurodegenerative diseases,” Dr. Freeman summed up.

ABOUT THE GSA DROSOPHILA RESEARCH CONFERENCE: Nearly 1,500 researchers attend the annual GSA Drosophila Research Conference to share the latest research using the fruit fly Drosophila melanogaster and other insect species. Many of findings from these model organisms have broad application for the study of human genetic traits and diseases. For more information about the conference, see http://www.dros-conf.org/2013/

ABOUT GSA: Founded in 1931, the Genetics Society of America (GSA) is the professional membership organization for scientific researchers, educators, bioengineers, bioinformaticians and others interested in the field of genetics. Its nearly 5,000 members work to advance knowledge in the basic mechanisms of inheritance, from the molecular to the population level. The GSA is dedicated to promoting research in genetics and to facilitating communication among geneticists worldwide through its conferences, including the biennial conference on Model Organisms to Human Biology, an interdisciplinary meeting on current and cutting edge topics in genetics research, as well as annual and biennial meetings that focus on the genetics of particular organisms, including C. elegans, Drosophila, fungi, mice, yeast, and zebrafish. GSA publishes GENETICS, a leading journal in the field and a new online, open-access publication, G3: Genes|Genomes|Genetics. For more information about GSA, please visit www.genetics-gsa.org. Also follow GSA on Facebook at facebook.com/GeneticsGSA and on Twitter @GeneticsGSA.

Phyllis Edelman | Newswise
Further information:
http://www.genetics-gsa.org

More articles from Life Sciences:

nachricht What happens in the cell nucleus after fertilization
06.12.2016 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Researchers uncover protein-based “cancer signature”
05.12.2016 | Universität Basel

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Significantly more productivity in USP lasers

In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.

Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...

Im Focus: Shape matters when light meets atom

Mapping the interaction of a single atom with a single photon may inform design of quantum devices

Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

Simple processing technique could cut cost of organic PV and wearable electronics

06.12.2016 | Materials Sciences

3-D printed kidney phantoms aid nuclear medicine dosing calibration

06.12.2016 | Medical Engineering

Robot on demand: Mobile machining of aircraft components with high precision

06.12.2016 | Power and Electrical Engineering

VideoLinks
B2B-VideoLinks
More VideoLinks >>>