Rutgers researcher Karl Herrup and colleagues at Case Western Reserve University have discovered that a protein that suppresses cell division in brain cells effectively "puts the brakes" on the dementia that comes with Alzheimer's disease (AD). When the brakes fail, dementia results.
This discovery could open the door to new ways of treating Alzheimer's disease, which affects up to half the population over the age of 85.
Determining the protein’s previously unsuspected role in AD is an important piece of the puzzle and it brings a new perspective to the basis of AD. “It changes the logic from a search for a trigger that kicks off the dementia to the failure of a safety that has suppressed it,” said Herrup, chair of the Department of Cell Biology and Neuroscience at Rutgers, The State University of New Jersey.
The researchers reported their findings in the in the June 24 Proceedings of the National Academy of Sciences (PNAS). The paper was previously available online in the PNAS Early Edition.
Herrup has spent a good part of his career seeking to unravel the mystery behind unrestrained cell cycling. Looking at AD through the lens of cancer, Herrup sees the rampant cell division associated with cancer mirrored in AD-related dementia.
In cancer, the seemingly uncontrollable cell division enables the disease to overwhelm normal body cells. Adult neurons, or nerve cells, don't normally divide. (Cancerous brain tumors do not grow from neurons but from glial cells.) Instead of producing new neurons in the brain, the cycling leads to cell death, which causes progressive dementia.
"Every cell wants to divide, and that basic urge never leaves the cell," Herrup said.
"Homeostasis in the brain has worked out a way to successfully suppress cell cycling, but with age even that highly successful program sometimes fails, resulting in a catastrophic loss of neurons."
Herrup's team experimented with a protein family known as cyclin-dependent kinases (Cdk). These enzymes power the cell cycle, driving it forward through its various phases. The scientists focused on one particular kinase – Cdk5 – termed "an atypical kinase" because they could find no involvement in propelling the cell cycle. They found that while it appears to be inert as a cell cycle promoter, Cdk5 in the nervous system actually functions to hold the cell cycle in check.
"Its mere presence helps protect the brain," Herrup said. "What we discovered is that Cdk5 acts as a brake, not a driver."
Their latest laboratory research examined the workings of Cdk5 in human AD tissues and in a mouse model. Normally, the protein resides in the nerve cell nucleus, but in the presence of AD – both in the mouse model and in the human tissue – the disease process drives the protein out into the cell's cytoplasm. This disrupts the status quo, overrides the brake and unleashes a chain of events that ultimately leads to the death of the cells and the resulting dementia.
"The ejection of Cdk5 out of the nucleus is probably related to the changed chemistry of the Alzheimer's brain and chronic inflammation that accompanies AD," Herrup said.
Joseph Blumberg | EurekAlert!
Scientists uncover the role of a protein in production & survival of myelin-forming cells
19.07.2018 | Advanced Science Research Center, GC/CUNY
NYSCF researchers develop novel bioengineering technique for personalized bone grafts
18.07.2018 | New York Stem Cell Foundation
A new manufacturing technique uses a process similar to newspaper printing to form smoother and more flexible metals for making ultrafast electronic devices.
The low-cost process, developed by Purdue University researchers, combines tools already used in industry for manufacturing metals on a large scale, but uses...
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
20.07.2018 | Power and Electrical Engineering
20.07.2018 | Information Technology
20.07.2018 | Materials Sciences