Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Scientists identify first gene in programmed axon degeneration

Discovery provides evidence of new therapeutic target that could delay axon decay

Degeneration of the axon and synapse, the slender projection through which neurons transmit electrical impulses to neighboring cells, is a hallmark of some of the most crippling neurodegenerative and brain diseases such as amyotrophic lateral sclerosis (ALS), Huntington's disease and peripheral neuropathy.

Scientists have worked for decades to understand axonal degeneration and its relation to these diseases. Now, researchers at the University of Massachusetts Medical School are the first to describe a gene – dSarm/Sarm1 – responsible for actively promoting axon destruction after injury. The research, published today online by Science, provides evidence of an exciting new therapeutic target that could be used to delay or even stop axon decay.

"This discovery has the potential to have a profound impact on our understanding of neurodegenerative diseases, much like the discovery of apoptosis (programmed cell death) fundamentally changed our understanding of cancer," said Marc R. Freeman, PhD, associate professor of neurobiology at the University of Massachusetts Medical School and lead investigator on the study. "Identification of this gene allows us to start asking exciting new questions about the role of axon death in neurodegenerative diseases. For example, is it possible that these pathways are being inappropriately activated to cause premature axon death?"

For more than a century, scientists believed that injured axons severed from the neuron cell body passively wasted away due to a lack of nutrients. However, a mouse mutation identified in the early 1990s – called slow Wallerian degeneration (Wlds) – was able to suppress axon degeneration for weeks. This finding forced scientists to reassess Wallerian degeneration, the process through which an injured axon degenerates, as a passive process and consider the possibility that an active program of axon auto-destruction, akin to apoptotic death, was at work instead.

If Wallerian degeneration was an active process, hypothesized Dr. Freeman, a Howard Hughes Medical Institute Early Career Scientist, then it should be possible through forward genetic screens in Drosophila to identify mutants exhibiting Wlds-like axon protection. Freeman and colleagues screened more than 2,000 Drosophila mutants for ones that exhibited long-term survival of severed axons. Freeman says this was a heroic effort on the part of his colleagues. The screen took place over the next two and a half years, and involved seven students and post-docs in the Freeman lab—Jeannette M. Osterloh, A. Nicole Fox, PhD, Michelle A. Avery, PhD, Rachel Hackett, Mary A. Logan, PhD, Jennifer M. MacDonald, Jennifer S. Zeigenfuss—who performed the painstaking and labor-intensive experiments needed on each Drosophila mutant to identify flies that suppressed axonal degeneration after nerve injury.

Through these tests, they identified three mutants (out of the 2,000 screened) where severed axons survived for the lifespan of the fly. Next generation sequencing and chromosome deficiency mapping techniques were then used to isolate the single gene affected in all three – dSarm. These were loss-of-function alleles, meaning that Drosophila unable to produce the dSarm/Sarm1 molecule exhibited prolonged axon survival for as many as 30 days after injury. Freeman and colleagues went on to show that mice lacking Sarm1, the mammalian homolog of dSarm, also displayed remarkable preservation of injured axons. These findings provided the first direct evidence that Wallerian degeneration was driven by a conserved axonal death program and not a passive response to axon injury.

"For 20 years people have been looking for a gene whose normal function is to promote axon degeneration," said Osterloh, first author on the study. "Identification of the dSarm/Sarm1 gene has enormous therapeutic potential, for example as a knockdown target for patients suffering from diseases involving axonal loss."

The next step for Freeman and colleagues is to identify additional genes in the axon death pathway and investigate whether any have links with specific neurodegenerative diseases. "We're already working with scientists at UMMS to understand the role axon death plays in ALS and Huntington's disease," said Freeman. "We are very excited about the possibility that these findings could have broad therapeutic potential in many neurodegenerative diseases."

About the University of Massachusetts Medical School

The University of Massachusetts Medical School, one of the fastest growing academic health centers in the country, has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $270 million in research funding annually, 80 percent of which comes from federal funding sources. The mission of the Medical School is to advance the health and well-being of the people of the commonwealth and the world through pioneering education, research, public service and health care delivery with its clinical partner, UMass Memorial Health Care.

Jim Fessenden | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich

nachricht Researchers Discover New Anti-Cancer Protein
22.03.2018 | 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: Researchers Discover New Anti-Cancer Protein

An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.

The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...

Im Focus: Researchers at Fraunhofer monitor re-entry of Chinese space station Tiangong-1

In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.

Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...

Im Focus: Alliance „OLED Licht Forum“ – Key partner for OLED lighting solutions

Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.

They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...

Im Focus: Mars' oceans formed early, possibly aided by massive volcanic eruptions

Oceans formed before Tharsis and evolved together, shaping climate history of Mars

A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...

Im Focus: Tiny implants for cells are functional in vivo

For the first time, an interdisciplinary team from the University of Basel has succeeded in integrating artificial organelles into the cells of live zebrafish embryos. This innovative approach using artificial organelles as cellular implants offers new potential in treating a range of diseases, as the authors report in an article published in Nature Communications.

In the cells of higher organisms, organelles such as the nucleus or mitochondria perform a range of complex functions necessary for life. In the networks of...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

Virtual reality conference comes to Reutlingen

19.03.2018 | Event News

Ultrafast Wireless and Chip Design at the DATE Conference in Dresden

16.03.2018 | Event News

International Tinnitus Conference of the Tinnitus Research Initiative in Regensburg

13.03.2018 | Event News

Latest News

Modular safety concept increases flexibility in plant conversion

22.03.2018 | Trade Fair News

New interactive map shows climate change everywhere in world

22.03.2018 | Earth Sciences

New technologies and computing power to help strengthen population data

22.03.2018 | Earth Sciences

Science & Research
Overview of more VideoLinks >>>