Featured Research

from universities, journals, and other organizations

Key enzyme involved in protecting nerves from degeneration identified

Date:
March 30, 2012
Source:
University of Pennsylvania
Summary:
A new animal model of nerve injury has brought to light a critical role of an enzyme called Nmnat in nerve fiber maintenance and neuroprotection. Understanding biological pathways involved in maintaining healthy nerves and clearing away damaged ones may offer scientists targets for drugs to mitigate neurodegenerative diseases such as Huntington's and Parkinson's, as well as aid in situations of acute nerve damage, such as spinal cord injury.

A new animal model of nerve injury has brought to light a critical role of an enzyme called Nmnat in nerve fiber maintenance and neuroprotection. Understanding biological pathways involved in maintaining healthy nerves and clearing away damaged ones may offer scientists targets for drugs to mitigate neurodegenerative diseases such as Huntington's and Parkinson's, as well as aid in situations of acute nerve damage, such as spinal cord injury.

University of Pennsylvanian biologists developed the model in the adult fruit fly, Drosophila melanogaster.

"We are using the basic power of the fly to learn about how neurons are damaged in acute injury situations," said Nancy Bonini, senior author of the research and a professor in the Department of Biology at Penn. "Our work indicates that Nmnat may be key."

The research was published in Current Biology. First author on the study is postdoctoral researcher Yanshan Fang, with additional contributions from postdoctoral researcher Lorena Soares and research technicians Xiuyin Teng and Melissa Geary, all of Penn's Department of Biology.

When a nerve suffers an acute injury -- as might be caused by a penetrating wound, for example, or a broken bone that damages nearby tissues -- the long projection of the nerve cell, called the axon, can become injured and degenerate. The process by which it disintegrates is known as Wallerian or Wallerian-like degeneration and is an active, orderly process.

Though this function of eliminating damaged nerve cells is crucial, biologists do not have a clear understanding of all of the molecular signaling pathways that govern the process.

Bonini's lab has previously focused on chronic neurodegenerative diseases but made this foray into acute nerve injury to determine if mechanistic overlaps exist between acute axon injury and chronic neurodegeneration. They first searched for an appropriate nerve tract to target and identified the wing of adult flies as a prime option.

The fly wing is not only translucent and a site of lengthy nerve fibers that can be easily observed, but it can also be cut to cause injury without killing the fly. That way, the researchers can follow the animal's response to nerve injury for weeks.

Using various reagents to manipulate the fly's genetic traits, the team confirmed that the cut wing nerve underwent Wallerian degeneration. They then tested versions of Nmnat and another protein called WldS, all of which had previously been shown to protect nerves from degeneration, to see if any of these might stop the process. All significantly delayed neurodegeneration. Even a form of Nmnat that hadn't worked in other animal models suppressed degeneration, although to a lesser extent.

"That indicates that our assay is really sensitive," Bonini said. "This sensitivity could help us identify genes that have moderate although important functionality at protecting against nerve degeneration."

Their investigations into the wing nerve also showed that the degenerating axon "died back," fragmenting first from the axon terminals, the side farthest from the nerve cell body -- a pattern similar to what has been seen in other disorders.

Doing more genetic tinkering, the researchers showed that when the animal's own Nmnat was depleted, the nerves fragmented in the same way as if the axon was physically cut. And when Nmnat and the other "rescue" proteins were added back to these genetically modified flies, they were able to block degeneration, highlighting that Nmnat is critical to maintaining healthy axons.

In a final set of experiments, the biologists sought to narrow where in the nerve cells Nmnat might be working. They focused on mitochondria, the powerhouses of cells. When they created a genetic line of flies that blocked mitochondria from entering the axon fibers, the nerve tract degenerated, again, in a dying-back fashion. Yet now WldS and Nmnat failed to prevent axon degeneration, suggesting that those proteins may act on and require the presence of axonal mitochondria to maintain healthy nerves in normal flies.

Flipping that scenario around, they looked to see what happened to the mitochondria of flies upon nerve injury. When they cut the wing nerve axons, the mitochondria rapidly disappeared. Yet they can largely preserve the mitochrondria by increasing expression of Nmnat.

Their results, taken together with the findings of other studies, suggest that Nmnat may stabilize mitochondria in some way in order to keep axons in a healthy state.

"We have some hope that these proteins or their activity may someday serve as drug targets or could provide the foundation for a therapeutic advance," Bonini said. "But right now, my hope is that the power of the fly model will open up a lot of new directions of research and new pathways that could be targets for development in the future."

This study was supported by the Howard Hughes Medical Institute, the Fidelity Foundation and the National Institutes of Health.


Story Source:

The above story is based on materials provided by University of Pennsylvania. Note: Materials may be edited for content and length.


Journal Reference:

  1. Yanshan Fang, Lorena Soares, Xiuyin Teng, Melissa Geary, NancyM. Bonini. A Novel Drosophila Model of Nerve Injury Reveals an Essential Role of Nmnat in Maintaining Axonal Integrity. Current Biology, 2012; DOI: 10.1016/j.cub.2012.01.065

Cite This Page:

University of Pennsylvania. "Key enzyme involved in protecting nerves from degeneration identified." ScienceDaily. ScienceDaily, 30 March 2012. <www.sciencedaily.com/releases/2012/03/120330164852.htm>.
University of Pennsylvania. (2012, March 30). Key enzyme involved in protecting nerves from degeneration identified. ScienceDaily. Retrieved August 1, 2014 from www.sciencedaily.com/releases/2012/03/120330164852.htm
University of Pennsylvania. "Key enzyme involved in protecting nerves from degeneration identified." ScienceDaily. www.sciencedaily.com/releases/2012/03/120330164852.htm (accessed August 1, 2014).

Share This




More Health & Medicine News

Friday, August 1, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Ebola Vaccine Might Be Coming, But Where's It Been?

Ebola Vaccine Might Be Coming, But Where's It Been?

Newsy (Aug. 1, 2014) Health officials are working to fast-track a vaccine — the West-African Ebola outbreak has killed more than 700. But why didn't we already have one? Video provided by Newsy
Powered by NewsLook.com
Study Links Certain Birth Control Pills To Breast Cancer

Study Links Certain Birth Control Pills To Breast Cancer

Newsy (Aug. 1, 2014) Previous studies have made the link between birth control and breast cancer, but the latest makes the link to high-estrogen oral contraceptives. Video provided by Newsy
Powered by NewsLook.com
House Republicans Vote to Sue Obama Over Healthcare Law

House Republicans Vote to Sue Obama Over Healthcare Law

Reuters - US Online Video (July 31, 2014) The Republican-led House of Representatives votes to sue President Obama, accusing him of overstepping his executive authority in making changes to the Affordable Care Act. Mana Rabiee reports. Video provided by Reuters
Powered by NewsLook.com
Uganda on Alert for Ebola but No Confirmed Cases

Uganda on Alert for Ebola but No Confirmed Cases

AFP (July 31, 2014) Uganda's health minister said on Thursday that there are no confirmed cases of Ebola in the country, but that it remained on alert for cases of the deadly virus. Uganda has suffered Ebola outbreaks in the past, most recently in 2012. Duration: 00:59 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:

Breaking News:
from the past week

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile: iPhone Android Web
Follow: Facebook Twitter Google+
Subscribe: RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins