Featured Research

from universities, journals, and other organizations

New direction in Alzheimer's research

Date:
June 7, 2011
Source:
University of California - Santa Barbara
Summary:
In what they are calling a new direction in the study of Alzheimer's disease, scientists have made an important finding about what happens to brain cells that are destroyed in Alzheimer's disease and related dementias.

Image of rat neurons growing in a culture dish. The purple spheres are the cell nuclei and the red corresponds to the localization of phosphorylated tau.X
Credit: Jack Reifert, UCSB

In what they are calling a new direction in the study of Alzheimer's disease, UC Santa Barbara scientists have made an important finding about what happens to brain cells that are destroyed in Alzheimer's disease and related dementias.

Related Articles


The results are published in the online version of The Journal of Biological Chemistry.

Stuart Feinstein, professor of Molecular, Cellular and Developmental Biology, senior author, and co-director of UCSB's Neuroscience Research Institute, explained: "With dementia, the brain cells, or neurons, that you need for cognitive skills are no longer working properly. Then, they're not even there anymore because they die. That's what leads to dementia; you're losing neuronal capacity."

Feinstein has studied the protein called "tau" for about 30 years, using test tube biochemistry and a variety of cultured cells as models. Under normal conditions, tau is found in the long axons of neurons that serve to connect neurons with their targets, often far from the cell body itself. Among tau's major functions is to stabilize microtubules, which are an integral part of the cellular cytoskeleton that is essential for many aspects of neuronal cell structure and function.

It has been known for many years that a small peptide named amyloid beta can cause neuronal cell death and Alzheimer's disease, although the mechanism for how it works has been poorly understood. Recently, genetic evidence has demonstrated that the ability of amyloid beta to kill neurons requires tau; however, what it does to tau has been enigmatic. "We know amyloid beta is a bad guy," said Feinstein. "Amyloid beta causes disease; amyloid beta causes Alzheimer's. The question is how does it do it?"

He explained that most Alzheimer's researchers would argue that amyloid beta causes tau to become abnormally and excessively phosphorylated. This means that the tau proteins get inappropriately chemically modified with phosphate groups. "Many of our proteins get phosphorylated," said Feinstein. "It can be done properly or improperly."

Feinstein added that he and his students wanted to determine the precise details of the presumed abnormal phosphorylation of tau in order to gain a better understanding of what goes wrong. "That would provide clues for drug companies; they would have a more precise target to work on," said Feinstein. "The more precisely they understand the biochemistry of the target, the better attack a pharmaceutical company can make on a problem."

Feinstein said that the team's initial hypothesis suggesting that amyloid beta leads to extensive abnormal tau phosphorylation turned out not to be true. "We all like to get a curve ball tossed our way once in a while, right?" said Feinstein. "You like to see something different and unexpected."

The research team found that when they added amyloid beta to neuronal cells, the tau in those cells did not get massively phosphorylated, as predicted. Rather, the surprising observation was the complete fragmentation of tau within one to two hours of exposure of the cells to amyloid beta. Within 24 hours, the cells were dead.

Feinstein explained that tau has many jobs, but its best-understood job is to regulate the cellular cytoskeleton. Cells have a skeleton much like humans have a skeleton. The major difference is that human skeletons don't change shape very abruptly, whereas a cell's skeleton is constantly growing, shortening, and moving. It does this in order to help the cell perform many of its essential functions. The cytoskeleton is especially important to neurons because of their great length.

Feinstein argues that neurons die in Alzheimer's disease because their cytoskeleton is not working properly. "If you destroy tau, which is an important regulator of the microtubules, one could easily see how that could also cause cell death," said Feinstein. "We know from cancer drugs that if you treat cells with drugs that disrupt the cytoskeleton, the cells die," he said. "In my mind, the same thing could be happening here."

The Feinstein lab is now at work on the implications of the experiments described in the article.

Co-authors of the article are graduate student Jack Reifert and former graduate student DeeAnn Hartung-Cranston.


Story Source:

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


Journal Reference:

  1. J. Reifert, D. Hartung-Cranston, S. C. Feinstein. Amyloid beta mediated cell death of cultured hippocampal neurons reveals extensive tau fragmentation without increased full-length tau phosphorylation. Journal of Biological Chemistry, 2011; DOI: 10.1074/jbc.M111.234674

Cite This Page:

University of California - Santa Barbara. "New direction in Alzheimer's research." ScienceDaily. ScienceDaily, 7 June 2011. <www.sciencedaily.com/releases/2011/06/110606161026.htm>.
University of California - Santa Barbara. (2011, June 7). New direction in Alzheimer's research. ScienceDaily. Retrieved December 22, 2014 from www.sciencedaily.com/releases/2011/06/110606161026.htm
University of California - Santa Barbara. "New direction in Alzheimer's research." ScienceDaily. www.sciencedaily.com/releases/2011/06/110606161026.htm (accessed December 22, 2014).

Share This


More From ScienceDaily



More Mind & Brain News

Monday, December 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

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
Researchers Test Colombian Village With High Alzheimer's Rates

Researchers Test Colombian Village With High Alzheimer's Rates

AFP (Dec. 19, 2014) In Yarumal, a village in N. Colombia, Alzheimer's has ravaged a disproportionately large number of families. A genetic "curse" that may pave the way for research on how to treat the disease that claims a new victim every four seconds. Duration: 02:42 Video provided by AFP
Powered by NewsLook.com
Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Double-Amputee Becomes First To Move Two Prosthetic Arms With His Mind

Buzz60 (Dec. 19, 2014) A double-amputee makes history by becoming the first person to wear and operate two prosthetic arms using only his mind. Jen Markham has the story. Video provided by Buzz60
Powered by NewsLook.com
Prenatal Exposure To Pollution Might Increase Autism Risk

Prenatal Exposure To Pollution Might Increase Autism Risk

Newsy (Dec. 18, 2014) Harvard researchers found children whose mothers were exposed to high pollution levels in the third trimester were twice as likely to develop autism. Video provided by Newsy
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