Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Experimental drug reverses key cognitive deficits, pathology in Alzheimer’s

02.03.2006


A new drug that enhances the activity of a key brain cell receptor involved in Alzheimer’s disease (AD) reverses learning and memory deficits in mice engineered to have pathological hallmarks of the disease. What’s more, the drug, called AF267B, reduces both of the pathologies--the brain-clogging buildup of protein "amyloid plaque" outside brain cells and the protein "neurofibrillary tangles" inside the cells.



In an article in the March 2, 2006, issue of Neuron, Dr. Frank LaFerla of the University of California, Irvine and his colleagues reported the first in vivo studies of the drug’s effects. AF267B was developed by coauthor Abraham Fisher to activate particular receptors for the neurotransmitter acetylcholine. These specific receptors, called M1 receptors, are abundant in areas of the brain--the cortex and hippocampus--known to develop severe deposits of plaques and tangles in AD patients. Dysfunction in acetylcholine receptors has been shown to be characteristic of early stages of AD.

Receptors are proteins on the neuronal surface that are triggered by the chemical signals called neurotransmitters. This triggering initiates such cellular responses as the wave of electrical excitation of a nerve impulse.


As an animal model of AD, the researchers used a "triple knockout" mouse in which three key genes involved in normal brain protein processing pathways had been knocked out, creating both amyloid plaques and neurofibrillary tangles.

In their experiments, the researchers gave the knockout mice eight weeks of daily doses of AF267B and tested the animals’ learning and memory abilities. One test involved measuring how well the treated animals could learn to find a submerged platform in a tank of murky water. This test is known to depend on the function of the hippocampus. The researchers found that the treated mice performed significantly better than untreated knockout mice on the task.

Significantly, found the researchers, the poorer performance of the untreated mice resulted from their relative inability to remember from day-to-day the location of the platform.

In another memory test, however, the treated mice did not show improved performance compared to untreated mice. In this test--which depends on the function of another Alzheimer’s-affected brain region called the amygdala--the mice were required to learn to associate a dark chamber with an unpleasant shock.

Analyzing the brain tissue of the untreated and treated mice, the researchers found that treatment with AF267B reduced levels of both pathological plaques and tangles in the cortex and hippocampus, but not in the amygdala.

In experiments that demonstrated the central role of M1 receptors in AD-like pathology, the researchers also tested the effects on the mice of another drug, dicyclomine, that blocks M1 receptors. They found that both normal and knockout mice treated with the drug showed the characteristic learning and memory impairments, as well as amyloid and tangle pathologies.

The researchers also studied the effects of AF267B treatment on key enzymes involved in amyloid protein processing in the cell. They found evidence that the drug appears to work by affecting levels of these enzymes, as a result of its enhancement of M1 receptor activity.

The researchers concluded that "the results of the present study show the remarkable therapeutic potential of AF267B in attenuating the major hallmark neuropathological lesions relevant to AD and in restoring cognitive function, at least for certain tasks." They also pointed out the importance of the finding that administering dicyclomine to block M1 receptors exacerbated the disease pathologies.

"Further work, including clinical trials in humans, will be necessary to determine if this new generation of M1 agonists will produce a similar therapeutic efficacy as was observed in the [knockout] mice," they concluded.

Heidi Hardman | EurekAlert!
Further information:
http://www.cell.com
http://www.neuron.org

More articles from Life Sciences:

nachricht The birth of a new protein
20.10.2017 | University of Arizona

nachricht Building New Moss Factories
20.10.2017 | Albert-Ludwigs-Universität Freiburg im Breisgau

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Neutron star merger directly observed for the first time

University of Maryland researchers contribute to historic detection of gravitational waves and light created by event

On August 17, 2017, at 12:41:04 UTC, scientists made the first direct observation of a merger between two neutron stars--the dense, collapsed cores that remain...

Im Focus: Breaking: the first light from two neutron stars merging

Seven new papers describe the first-ever detection of light from a gravitational wave source. The event, caused by two neutron stars colliding and merging together, was dubbed GW170817 because it sent ripples through space-time that reached Earth on 2017 August 17. Around the world, hundreds of excited astronomers mobilized quickly and were able to observe the event using numerous telescopes, providing a wealth of new data.

Previous detections of gravitational waves have all involved the merger of two black holes, a feat that won the 2017 Nobel Prize in Physics earlier this month....

Im Focus: Smart sensors for efficient processes

Material defects in end products can quickly result in failures in many areas of industry, and have a massive impact on the safe use of their products. This is why, in the field of quality assurance, intelligent, nondestructive sensor systems play a key role. They allow testing components and parts in a rapid and cost-efficient manner without destroying the actual product or changing its surface. Experts from the Fraunhofer IZFP in Saarbrücken will be presenting two exhibits at the Blechexpo in Stuttgart from 7–10 November 2017 that allow fast, reliable, and automated characterization of materials and detection of defects (Hall 5, Booth 5306).

When quality testing uses time-consuming destructive test methods, it can result in enormous costs due to damaging or destroying the products. And given that...

Im Focus: Cold molecules on collision course

Using a new cooling technique MPQ scientists succeed at observing collisions in a dense beam of cold and slow dipolar molecules.

How do chemical reactions proceed at extremely low temperatures? The answer requires the investigation of molecular samples that are cold, dense, and slow at...

Im Focus: Shrinking the proton again!

Scientists from the Max Planck Institute of Quantum Optics, using high precision laser spectroscopy of atomic hydrogen, confirm the surprisingly small value of the proton radius determined from muonic hydrogen.

It was one of the breakthroughs of the year 2010: Laser spectroscopy of muonic hydrogen resulted in a value for the proton charge radius that was significantly...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ASEAN Member States discuss the future role of renewable energy

17.10.2017 | Event News

World Health Summit 2017: International experts set the course for the future of Global Health

10.10.2017 | Event News

Climate Engineering Conference 2017 Opens in Berlin

10.10.2017 | Event News

 
Latest News

Terahertz spectroscopy goes nano

20.10.2017 | Information Technology

Strange but true: Turning a material upside down can sometimes make it softer

20.10.2017 | Materials Sciences

NRL clarifies valley polarization for electronic and optoelectronic technologies

20.10.2017 | Interdisciplinary Research

VideoLinks
B2B-VideoLinks
More VideoLinks >>>