Featured Research

from universities, journals, and other organizations

Preventing 'traffic jams' in brain cells

Date:
May 28, 2013
Source:
University at Buffalo
Summary:
An Alzheimer’s disease protein controls the speed at which materials move through brain cells, and defects could lead to deadly pileups of the kind seen in neurodegenerative disease, a new publication finds.

Expression of human APP in fly larval nerves causes axonal blockages (arrows, top panel) which are rescued by reductions in presenilin. Expression of human APP in fly larval brains causes cell death (arrows, bottom panel) which are rescued by reductions in presenilin.
Credit: Shermali Gunawardena

Imagine if you could open up your brain and look inside.

Related Articles


What you would see is a network of nerve cells called neurons, each with its own internal highway system for transporting essential materials between different parts of the cell.

When this biological machinery is operating smoothly, tiny motor proteins ferry precious cargo up and down each neuron along thread-like roadways called microtubule tracks. Brain cells are able to receive information, make internal repairs and send instructions to the body, telling the fingers to flex or the toes to curl.

But when the neuron gets blocked, this delicate harmony deteriorates. One result: diseases like Alzheimer's.

Understanding such blockages and how traffic should flow normally in healthy brain cells could offer hope to people with neurodegenerative diseases.

Toward that end, a research team led by University at Buffalo biologist Shermali Gunawardena, PhD, has shown that the protein presenilin plays an important role in controlling neuronal traffic on microtubule highways, a novel function that previously was unknown.

The research results were published May 24 in the journal Human Molecular Genetics. Gunawardena's co-authors are Ge Yang of Carnegie Mellon University and Lawrence S. B. Goldstein of the Howard Hughes Medical Institute and the University of California, San Diego.

Inside the nerves of fruit fly larvae, presenilin helped to control the speed at which molecular motors called kinesins and dyneins moved along neurons. When the scientists halved the amount of presenilin present in the highway system, the motors moved faster; they paused fewer times and their pauses were shorter.

Given this data, Gunawardena thinks that tweaking presenilin levels may be one way to free up traffic and prevent dangerous neuronal blockages in patients with Alzheimer's disease.

"Our major discovery is that presenilin has a novel role, which is to control the movement of motor proteins along neuronal highways," said Gunawardena, an assistant professor of biological sciences. "If this regulation/control is lost, then things can go wrong. This is the first time a protein that functions as a controller of motors has been reported.

"In Alzheimer's disease, transport defects occur well before symptoms, such as cell death and amyloid plaques, are seen in post-mortem brains," she added. "As a result, developing therapeutics targeted to defects in neuronal transport would be a useful way to attack the problem early."

To see a video of traffic flowing normally in a fruit fly larval nerve, visit http://www.youtube.com/watch?v=sWTKZwHwdBg

The findings are particularly intriguing because scientists have known for several years that presenilin is involved in Alzheimer's disease.

Presenilin rides along neuronal highways in tiny organic bubbles called vesicles that sit atop the kinesin and dynein motors, and also contain a second protein called the amyloid precursor protein (APP). Presenilin participates in cutting APP into pieces called amyloid beta, which build up to form amyloid plaques in patients with Alzheimer's disease.

Such buildups can lead to cell death by preventing the transport of essential materials -- like proteins needed for cell repair -- along neurons.

The findings of the new study mean that presenilin may contribute to Alzheimer's disease in at least two ways: not just by cleaving APP, but also by regulating the speed of the molecular motors that carry APP along neuronal highways.

"More than 150 mutations in presenilin have been identified in Alzheimer's disease," Gunawardena said. "Thus, understanding its function is important to understanding what goes wrong in Alzheimer's disease."

To track the movement of the kinesins and dyneins, the team tagged their cargo with a yellow fluorescent protein. This enabled the scientists to view the molecular motors chugging along inside the neuron under a microscope in a living animal. A special computer program then analyzed the motors' paths, revealing more details about the nature of their movement and how often they paused.


Story Source:

The above story is based on materials provided by University at Buffalo. The original article was written by Charlotte Hsu. Note: Materials may be edited for content and length.


Journal Reference:

  1. S. Gunawardena, G. Yang, L. S. B. Goldstein. Presenilin controls kinesin-1 and dynein function during APP vesicle transport in vivo. Human Molecular Genetics, 2013; DOI: 10.1093/hmg/ddt237

Cite This Page:

University at Buffalo. "Preventing 'traffic jams' in brain cells." ScienceDaily. ScienceDaily, 28 May 2013. <www.sciencedaily.com/releases/2013/05/130528143621.htm>.
University at Buffalo. (2013, May 28). Preventing 'traffic jams' in brain cells. ScienceDaily. Retrieved December 29, 2014 from www.sciencedaily.com/releases/2013/05/130528143621.htm
University at Buffalo. "Preventing 'traffic jams' in brain cells." ScienceDaily. www.sciencedaily.com/releases/2013/05/130528143621.htm (accessed December 29, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Monday, December 29, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

The Weirdest Health Studies Of 2014

The Weirdest Health Studies Of 2014

Newsy (Dec. 27, 2014) One of this year's strangest studies found people prefer painful electric shocks to being alone with their thoughts. Video provided by Newsy
Powered by NewsLook.com
When Healthy Eating Becomes Dangerous

When Healthy Eating Becomes Dangerous

Newsy (Dec. 26, 2014) Experts say fad diets can lead to orthorexia, a disorder that can cause physical and emotional distress. Video provided by Newsy
Powered by NewsLook.com
Are Paper Books Better Than E-Books For Sleep Cycle?

Are Paper Books Better Than E-Books For Sleep Cycle?

Newsy (Dec. 23, 2014) A study from Harvard Medical School shows that electronic readers utilizing LED technology interrupt people's natural sleep cycles. Video provided by Newsy
Powered by NewsLook.com
Brain-Dwelling Tapeworm Reveals Genetic Secrets

Brain-Dwelling Tapeworm Reveals Genetic Secrets

Reuters - Innovations Video Online (Dec. 22, 2014) Cambridge scientists have unravelled the genetic code of a rare tapeworm that lived inside a patient's brain for at least four year. Researchers hope it will present new opportunities to diagnose and treat this invasive parasite. Matthew Stock reports. Video provided by Reuters
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:

Strange & Offbeat Stories


Health & Medicine

Mind & Brain

Living & Well

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