Navigation Links
Neuroscientists identify protein linked to Alzheimer's-like afflictions
Date:8/11/2013

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 Universit de la Mditerrane 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.


'/>"/>

Contact: James Devitt
james.devitt@nyu.edu
212-998-6808
New York University
Source:Eurekalert

Related biology news :

1. Neuroscientists prove ultrasound can be tweaked to stimulate different sensations
2. UCI neuroscientists create fiber-optic method of arresting epileptic seizures
3. CSHL neuroscientists show jumping genes may contribute to aging-related brain defects
4. Carnegie Mellon neuroscientists discover new phase of synaptic development
5. Beyond the microscope: Identifying specific cancers using molecular analysis
6. Researchers identify new regulator in allergic diseases
7. Penn biologists identify a key enzyme involved in protecting nerves from degeneration
8. Researchers identify genes that may help in ovarian cancer diagnosis and prognosis
9. Researchers identify Achilles heel of dengue virus, target for future vaccines
10. BUSM researchers identify key regulator of inflammatory response
11. BUSM researchers identify genes that influence hippocampal volume
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:11/19/2016)... , Nov. 18, 2016 Securus Technologies, ... solutions for public safety, investigation, corrections and monitoring, announced ... smaller competitor, ICSolutions, to have an independent technology judge ... the most modern high tech/sophisticated telephone calling platform, and ... customers that they do most of what we do ...
(Date:11/15/2016)... , Nov 15, 2016 Research and Markets ... Forecast to 2021" report to their offering. ... ... 16.18 Billion by 2021 from USD 6.21 Billion in 2016, growing ... Growth of the bioinformatics market is driven by the growing ...
(Date:6/22/2016)... ANGELES , June 22, 2016 /PRNewswire/ ... identity management and verification solutions, has partnered ... edge software solutions for Visitor Management, Self-Service ... provides products that add functional enhancements ... partnership provides corporations and venues with an ...
Breaking Biology News(10 mins):
(Date:12/8/2016)...  Biotheranostics today announced that new data will ... Cancer Index (BCI) in identifying which patients with ... for disease recurrence and might benefit from extended ... advancing the understanding of the value of BCI ... inform decisions related to patient treatment. These data ...
(Date:12/8/2016)... Portland, Oregon (PRWEB) , ... December 08, 2016 ... ... modules and the FrontPanel SDK that provide essential device-to-computer interconnect using USB or ... do not require FrontPanel support. The FOMD-ACV-A4 is a small, thin, SODIMM-style module ...
(Date:12/8/2016)... ... 08, 2016 , ... KBioBox llc announced today the launch ... developed a sophisticated “3 click” gene dditing off target analysis program and a ... https://www.kbiobox.com/ and powered by the company’s proprietary BioEngine. Scientists, pharmaceutical ...
(Date:12/8/2016)... N.J. , Dec. 8, 2016  Soligenix, ... late-stage biopharmaceutical company focused on developing and commercializing ... an unmet medical need, announced today the long-term ... with SGX942 (dusquetide), a first-in-class Innate Defense Regulator ... in head and neck cancer patients undergoing chemoradiation ...
Breaking Biology Technology: