Featured Research

from universities, journals, and other organizations

Neuroscientists identify protein linked to Alzheimer's-like afflictions

Date:
August 11, 2013
Source:
New York University
Summary:
A team of neuroscientists has identified a modification to a protein in laboratory mice linked to conditions associated with Alzheimer’s Disease. Their findings also point to a potential therapeutic intervention for alleviating memory-related disorders.

A team of neuroscientists has identified a modification to a protein in laboratory mice linked to conditions associated with Alzheimer's Disease. Their findings, which appear in the journal Nature Neuroscience, also point to a potential therapeutic intervention for alleviating memory-related disorders.

The research centered on eukaryotic initiation factor 2 alpha (eIF2alpha) and two enzymes that modify it with a phosphate group; this type of modification is termed phosphorylation. The phosphorylation of eIF2alpha, which decreases protein synthesis, was previously found at elevated levels in both humans diagnosed with Alzheimer's and in Alzheimer's Disease (AD) model mice.

"These results implicate the improper regulation of this protein in Alzheimer's-like afflictions and offer new guidance in developing remedies to address the disease," said Eric Klann, a professor in New York University's Center for Neural Science and the study's senior author.

The study's co-authors also included: Douglas Cavener, a professor of biology at Pennsylvania State University; Clarisse Bourbon, Evelina Gatti, and Philippe Pierre of Université de la Méditerranée in Marseille, France; and NYU researchers Tao Ma, Mimi A. Trinh, and Alyse J. Wexler.

It has been known for decades that triggering new protein synthesis is vital to the formation of long-term memories as well as for long-lasting synaptic plasticity -- the ability of the neurons to change the collective strength of their connections with other neurons. Learning and memory are widely believed to result from changes in synaptic strength.

In recent years, researchers have found that both humans with Alzheimer's Disease and AD model mice have relatively high levels of eIF2alpha phosphorylation. But the relationship between this characteristic and AD-related afflictions was unknown.

Klann and his colleagues hypothesized that abnormally high levels of eIF2alpha phosphorylation could become detrimental because, ultimately, protein synthesis would diminish, thereby undermining the ability to form long-term memories.

To explore this question, the researchers examined the neurological impact of two enzymes that phosphorylate eIF2alpha, kinases termed PERK and GCN2, in different populations of AD model mice -- all of which expressed genetic mutations akin to those carried by humans with AD. These were: AD model mice; AD model mice that lacked PERK; and AD model mice that lacked GCN2.

Specifically, they looked at eIF2alpha phosphorylation and the regulation of protein synthesis in the mice's hippocampus region -- the part of the brain responsible for the retrieval of old memories and the encoding of new ones. They then compared these levels with those of postmortem human AD patients.

Here, they found both increased levels of phosphorylated eIF2alpha in the hippocampus of both AD patients and the AD model mice. Moreover, in conjunction with these results, they found decreased protein synthesis, known to be required for long-term potentiation -- a form of long-lasting synaptic plasticity -- and for long-term memory.

To test potential remedies, the researchers examined phosphorylation of eIF2alpha in mice lacking PERK, hypothesizing that removal of this kinase would return protein synthesis to normal levels. As predicted, mice lacking PERK had levels of phosphorylated eIF2alpha and protein synthesis similar to those of normal mice.

They then conducted spatial memory tests in which the mice needed to navigate a series of mazes. Here, the AD model mice lacking PERK were able to successfully maneuver through the mazes at rates achieved by normal mice. By contrast, the other AD model mice lagged significantly in performing these tasks.

The researchers replicated these procedures on AD model mice lacking GCN2. The results here were consistent with those of the AD model mice lacking PERK, demonstrating that removal of both kinases diminished memory deficits associated with Alzheimer's Disease.

The research was supported by grants from the National Institutes of Health (NS034007 and NS047834) and from the Alzheimer's Association.


Story Source:

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


Journal Reference:

  1. Tao Ma, Mimi A Trinh, Alyse J Wexler, Clarisse Bourbon, Evelina Gatti, Philippe Pierre, Douglas R Cavener, Eric Klann. Suppression of eIF2α kinases alleviates Alzheimer's disease–related plasticity and memory deficits. Nature Neuroscience, 2013; DOI: 10.1038/nn.3486

Cite This Page:

New York University. "Neuroscientists identify protein linked to Alzheimer's-like afflictions." ScienceDaily. ScienceDaily, 11 August 2013. <www.sciencedaily.com/releases/2013/08/130811150545.htm>.
New York University. (2013, August 11). Neuroscientists identify protein linked to Alzheimer's-like afflictions. ScienceDaily. Retrieved October 22, 2014 from www.sciencedaily.com/releases/2013/08/130811150545.htm
New York University. "Neuroscientists identify protein linked to Alzheimer's-like afflictions." ScienceDaily. www.sciencedaily.com/releases/2013/08/130811150545.htm (accessed October 22, 2014).

Share This



More Health & Medicine News

Wednesday, October 22, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Orthodontist Mom Jennifer Salzer on the Best Time for Braces

Working Mother (Oct. 22, 2014) — Is your child ready? Video provided by Working Mother
Powered by NewsLook.com
U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

U.S. Issues Ebola Travel Restrictions, Are Visa Bans Next?

Newsy (Oct. 22, 2014) — Now that the U.S. is restricting travel from West Africa, some are dropping questions about a travel ban and instead asking about visa bans. Video provided by Newsy
Powered by NewsLook.com
US to Track Everyone Coming from Ebola Nations

US to Track Everyone Coming from Ebola Nations

AP (Oct. 22, 2014) — Stepping up their vigilance against Ebola, federal authorities said Wednesday that everyone traveling into the US from Ebola-stricken nations will be monitored for symptoms for 21 days. (Oct. 22) Video provided by AP
Powered by NewsLook.com
Doctors Help Paralysed Man Walk Again, Patient in Disbelief

Doctors Help Paralysed Man Walk Again, Patient in Disbelief

AFP (Oct. 22, 2014) — Polish doctors describe how they helped a paralysed man walk again, with the patient in disbelief at the return of sensation to his legs. Duration: 1:04 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:

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