Navigation Links
Scientists identify first gene in programmed axon degeneration
Date:6/7/2012

WORCESTER, MA 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 labJeannette M. Osterloh, A. Nicole Fox, PhD, Michelle A. Avery, PhD, Rachel Hackett, Mary A. Logan, PhD, Jennifer M. MacDonald, Jennifer S. Zeigenfusswho 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."


'/>"/>
Contact: Jim Fessenden
james.fessenden@umassmed.edu
508-856-2000
University of Massachusetts Medical School
Source:Eurekalert

Related biology news :

1. UC Davis scientists find new role for P53 genetic mutation -- initiation of prostate cancer
2. OU scientists and international team deciper the genetic code of the tomato
3. Scientists discover a new sensory organ in the chin of baleen whales
4. Scientists start explaining Fat Bastards vicious cycle
5. Scientists find gold-plated fossil solution
6. New study by WHOI scientists provides baseline measurements of carbon in Arctic Ocean
7. Novel discovery by NUS scientists paves the way for more effective treatment of cancers
8. Stanford scientists document fragile land-sea ecological chain
9. Using graphene, scientists develop a less toxic way to rust-proof steel
10. Scripps Florida scientists awarded $8.4 million grant to develop new anti-smoking treatments
11. Berkeley Lab scientists generate electricity from viruses
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/16/2017)... 2017  Veratad Technologies, LLC ( www.veratad.com ), an ... identity verification solutions, announced today they will participate as ... 15 thru May 17, 2017, in Washington ... Center. Identity impacts the lives of ... quickly evolving digital world, defining identity is critical to ...
(Date:5/6/2017)... May 5, 2017 RAM Group ... a new breakthrough in biometric authentication based on ... mechanical properties to perform biometric authentication. These new sensors ... material created by Ram Group and its partners. This ... transportation, supply chains and security. Ram Group is ...
(Date:4/19/2017)... New York , April 19, 2017 ... competitive, as its vendor landscape is marked by the ... the market is however held by five major players ... Safran. Together these companies accounted for nearly 61% of ... of the leading companies in the global military biometrics ...
Breaking Biology News(10 mins):
(Date:10/12/2017)... ... October 12, 2017 , ... AMRI, a global contract ... to improve patient outcomes and quality of life, will now be offering its ... attributed to new regulatory requirements for all new drug products, including the finalization ...
(Date:10/11/2017)... , ... October 11, 2017 , ... ComplianceOnline’s Medical Device ... on 7th and 8th June 2018 in San Francisco, CA. The Summit brings together ... as several distinguished CEOs, board directors and government officials from around the world to ...
(Date:10/11/2017)... , ... October 11, 2017 , ... ... the implantation and pregnancy rates in frozen and fresh in vitro fertilization ... progesterone and maternal age to IVF success. , After comparing the results from ...
(Date:10/10/2017)... ... October 10, 2017 , ... Dr. Bob Harman, founder ... local San Diego Rotary Club. The event entitled “Stem Cells and ... had 300+ attendees. Dr. Harman, DVM, MPVM was joined by two human doctors: ...
Breaking Biology Technology: