Featured Research

from universities, journals, and other organizations

Scientists Find New Causes For Neurodegeneration

Date:
October 28, 2007
Source:
University of Michigan
Summary:
Diseases that cause neurons to break down, such as Alzheimer's, continue to be elusive to scientists and resistant to treatments. A new finding demonstrates an unpredicted link between a virtually unknown signaling molecule and neuron health. Scientists connect the loss of this molecule to massive neurodegeneration in the brain, which plays a key role in the survival of nervous system cells.

A small region of a mutant mouse brain magnified 1000X. In the normal tissue the cells are tightly packed with no gaps, but in the mutant there are large holes due to loss of neurons from absence of the molecule PI(3,5)P2 from suppression of the Vac14 gene.
Credit: Image courtesy of University of Michigan

Diseases that cause neurons to break-down, such as Alzheimer's, Multiple Sclerosis and Creutzfeldt-Jakob disease (Mad Cow Disease), continue to be elusive to scientists and resistant to treatments.

A new finding from University of Michigan researchers demonstrates an unpredicted link between a virtually unknown signaling molecule and neuron health.

In a study in PNAS, graduate student, Yanling Zhang, postdoctoral fellow Sergey Zolov and Life Sciences Institute professor Lois Weisman connect the loss of this molecule to massive neurodegeneration in the brain.

The molecule PI(3,5)P2 is a lipid found in all cells at very low levels. Lipids are a group of small organic compounds. While the best studied lipids are fats, waxes and oils, PI3,5P2 is a member of a unique class of lipids that signal the cell to perform special tasks.

Weisman said it was surprising to find that PI(3,5)P2 plays a key role in the survival of nervous system cells.

"In mice, lowered levels of PI(3,5)P2 leads to profound neurodegeneration," said Weisman. "It suggests that we have a good place to look to find treatments for neurodegenerative diseases such as Alzheimer's."

Weisman, who is also professor of Cell & Developmental Biology at the U-M Medical School and her colleagues, began from clues that were hidden in a conserved genetic pathway in yeast (a pathway that has remained the same in yeast, plants and humans over evolutionary time). Studies in yeast showed that the enzyme that manufactures the lipid is governed by the FIG4 and VAC14 genes, which exist in yeast, mice and humans.

Working with two independently derived mouse models, Weisman's team and collaborators including graduate student Clement Chow and Professor Miriam Meisler of the Department of Human Genetics at the U-M Medical School, reached the same conclusions in a pair of important papers for neuroscience research.

Building on research from Meisler, a mouse geneticist, and Weisman, a yeast geneticist, the collaborators published a paper in Nature, July 5, 2007, showing that in mice, the FIG4 gene is required to maintain normal levels of the signaling lipid and to maintain a normal nervous system. Importantly, they found that human patients with a very minor defect in their FIG4 genes had serious neurological problems.

The signaling lipid PI(3,5)P2 (short for phosphatidylinositol 3,5-bisphosphate) is part of a communication cascade that senses changes outside the cell and promotes actions inside the cell to accommodate to the changes.

Weisman's team found that mice missing the VAC14 gene, which encodes a regulator of PI(3,5)P2 levels, suffer massive neurodegeneration that looks nearly identical to the neurodegeneration seen in the FIG4 mutant mice. In both cases the levels of PI(3,5)P2 are one half of the normal levels. The fact that both mice have half the normal levels of the lipid and also have the same neurodegenerative problems provides evidence that there is a direct link between the lipid and neuronal health.

The new findings indicate that when Vac14 is removed, the cell bodies of many of the neurons appear to be empty spaces and the brain takes on a spongiform appearance.

The paper appearing in the online version of the Proceedings of the National Academy of Sciences October 22, 2007 is "Loss of Vac14, a regulator of the signaling lipid phosphatidylinositol 3,5-bisphosphate, results in neurodegeneration in mice," by a team of collaborators from U-M: Yanling Zhang, Sergey N. Zolov, Clement Y. Chow, Shalom G. Slutsky, Randal J. Westrick, Sean J. Morrison, Miriam H. Meisler, and Lois S. Weisman and the University of Iowa: Simon C. Richardson, Robert C. Piper, Baoli Yang, and Johnathan J. Nau.

The previous paper "Mutation of FIG4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J," was published in Nature on-line, June 17, 2007.


Story Source:

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


Cite This Page:

University of Michigan. "Scientists Find New Causes For Neurodegeneration." ScienceDaily. ScienceDaily, 28 October 2007. <www.sciencedaily.com/releases/2007/10/071025091040.htm>.
University of Michigan. (2007, October 28). Scientists Find New Causes For Neurodegeneration. ScienceDaily. Retrieved July 22, 2014 from www.sciencedaily.com/releases/2007/10/071025091040.htm
University of Michigan. "Scientists Find New Causes For Neurodegeneration." ScienceDaily. www.sciencedaily.com/releases/2007/10/071025091040.htm (accessed July 22, 2014).

Share This




More Health & Medicine News

Tuesday, July 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

Gilead's $1000-a-Pill Drug Could Cure Hep C in HIV-Positive People

TheStreet (July 21, 2014) New research shows Gilead Science's drug Sovaldi helps in curing hepatitis C in those who suffer from HIV. In a medical study, the combination of Gilead's Hep C drug with anti-viral drug Ribavirin cured 76% of HIV-positive patients suffering from the most common hepatitis C strain. Hepatitis C and related complications have been a top cause of death in HIV-positive patients. Typical medication used to treat the disease, including interferon proteins, tended to react badly with HIV drugs. However, Sovaldi's %1,000-a-pill price tag could limit the number of patients able to access the treatment. TheStreet's Keris Lahiff reports from New York. Video provided by TheStreet
Powered by NewsLook.com
$23.6 Billion Awarded To Widow In Smoking Lawsuit

$23.6 Billion Awarded To Widow In Smoking Lawsuit

Newsy (July 20, 2014) Cynthia Robinson claims R.J. Reynolds Tobacco Company hid the health and addiction risks of its products, leading to the death of her husband in 1996. Video provided by Newsy
Powered by NewsLook.com
Tooth Plaque Provides Insight Into Diets Of Ancient People

Tooth Plaque Provides Insight Into Diets Of Ancient People

Newsy (July 19, 2014) Research on plaque from ancient teeth shows that our prehistoric ancestor's had a detailed understanding of plants long before developing agriculture. Video provided by Newsy
Powered by NewsLook.com
Contaminated Water Kills 3 Babies in South African Town

Contaminated Water Kills 3 Babies in South African Town

AFP (July 18, 2014) Contaminated water in South Africa's northwestern town of Bloemhof kills three babies and hospitalises over 500 people. The incident highlights growing fears over water safety in South Africa. Duration: 02:22 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