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 New contents: Neuronal Parkinson inclusions are different than expected
26.06.2019 | Universität Basel

nachricht An ion channel with a doorkeeper: The pH of calcium ions controls ion channel opening
25.06.2019 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Fraunhofer IDMT demonstrates its method for acoustic quality inspection at »Sensor+Test 2019« in Nürnberg

From June 25th to 27th 2019, the Fraunhofer Institute for Digital Media Technology IDMT in Ilmenau (Germany) will be presenting a new solution for acoustic quality inspection allowing contact-free, non-destructive testing of manufactured parts and components. The method which has reached Technology Readiness Level 6 already, is currently being successfully tested in practical use together with a number of industrial partners.

Reducing machine downtime, manufacturing defects, and excessive scrap

Im Focus: Successfully Tested in Praxis: Bidirectional Sensor Technology Optimizes Laser Material Deposition

The quality of additively manufactured components depends not only on the manufacturing process, but also on the inline process control. The process control ensures a reliable coating process because it detects deviations from the target geometry immediately. At LASER World of PHOTONICS 2019, the Fraunhofer Institute for Laser Technology ILT will be demonstrating how well bi-directional sensor technology can already be used for Laser Material Deposition (LMD) in combination with commercial optics at booth A2.431.

Fraunhofer ILT has been developing optical sensor technology specifically for production measurement technology for around 10 years. In particular, its »bd-1«...

Im Focus: The hidden structure of the periodic system

The well-known representation of chemical elements is just one example of how objects can be arranged and classified

The periodic table of elements that most chemistry books depict is only one special case. This tabular overview of the chemical elements, which goes back to...

Im Focus: MPSD team discovers light-induced ferroelectricity in strontium titanate

Light can be used not only to measure materials’ properties, but also to change them. Especially interesting are those cases in which the function of a material can be modified, such as its ability to conduct electricity or to store information in its magnetic state. A team led by Andrea Cavalleri from the Max Planck Institute for the Structure and Dynamics of Matter in Hamburg used terahertz frequency light pulses to transform a non-ferroelectric material into a ferroelectric one.

Ferroelectricity is a state in which the constituent lattice “looks” in one specific direction, forming a macroscopic electrical polarisation. The ability to...

Im Focus: Determining the Earth’s gravity field more accurately than ever before

Researchers at TU Graz calculate the most accurate gravity field determination of the Earth using 1.16 billion satellite measurements. This yields valuable knowledge for climate research.

The Earth’s gravity fluctuates from place to place. Geodesists use this phenomenon to observe geodynamic and climatological processes. Using...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

Shell increases versatility of nanowires

26.06.2019 | Materials Sciences

Hubble finds tiny 'electric soccer balls' in space, helps solve interstellar mystery

26.06.2019 | Physics and Astronomy

New combination therapy established as safe and effective for prostate cancer

26.06.2019 | Health and Medicine

VideoLinks
Science & Research
Overview of more VideoLinks >>>