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
James Devitt | EurekAlert!
Improving memory with magnets
28.03.2017 | McGill University
Graphene-based neural probes probe brain activity in high resolution
28.03.2017 | Graphene Flagship
The Institute of Semiconductor Technology and the Institute of Physical and Theoretical Chemistry, both members of the Laboratory for Emerging Nanometrology (LENA), at Technische Universität Braunschweig are partners in a new European research project entitled ChipScope, which aims to develop a completely new and extremely small optical microscope capable of observing the interior of living cells in real time. A consortium of 7 partners from 5 countries will tackle this issue with very ambitious objectives during a four-year research program.
To demonstrate the usefulness of this new scientific tool, at the end of the project the developed chip-sized microscope will be used to observe in real-time...
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
28.03.2017 | Life Sciences
28.03.2017 | Information Technology
28.03.2017 | Physics and Astronomy