Navigation Links
Experimental drug reverses key cognitive deficits, pathology in Alzheimer's

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.


'"/>

Source:Cell Press


Related biology news :

1. NIAID Initiates Trial of Experimental Avian Flu Vaccine
2. Experimental shingles vaccine proves effective in nationwide study
3. Experimental vaccine protects nonhuman primates when given after exposure to Marburg virus
4. Experimental TB drug effective against resistant and latent mycobacterium tuberculosis
5. Experimental RNA-based drug kills prostate cancer cells effectively and safely
6. Experimental vaccine protects lab animals against several strains of H5N1
7. Experimental vaccine protects mice against deadly 1918 flu virus
8. Experimental cancer drugs counter muscle deterioration seen in muscular dystrophy
9. Experimental vaccine given during pregnancy reduces stillbirths from common virus
10. Muscle-targeted gene therapy reverses rare muscular dystrophy in mice
11. Genetic therapy reverses nervous system damage in animal model of inherited human disease
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:4/15/2016)... , April 15, 2016  A new partnership ... more accurate underwriting decisions in a fraction of ... competitively priced and high-value life insurance policies to ... With Force Diagnostics, rapid testing (A1C, ... data readings (blood pressure, weight, pulse, BMI, and ...
(Date:3/31/2016)... , March 31, 2016  Genomics firm Nabsys has ... CEO, Barrett Bready , M.D., who returned to ... the original technical leadership team, including Chief Technology Officer, ... Product Development, Steve Nurnberg and Vice President of Software ... the company. Dr. Bready served as CEO ...
(Date:3/21/2016)... , March 22, 2016 ... recognition with passcodes for superior security   ... a leading provider of secure digital communications services, today ... biometric technology and offer enterprise customers, particularly those in ... facial recognition and voice authentication within a mobile app, ...
Breaking Biology News(10 mins):
(Date:5/25/2016)... Oregon (PRWEB) , ... May 25, 2016 , ... ... Set features a variety of fracture-specific plating options designed to address fractures of ... industry-leading fracture fixation solutions. , The Acumed Ankle Plating System 3 is composed ...
(Date:5/25/2016)... ... ... Lady had been battling arthritis since the age of two and at the ... Hannah sought the help of Dr Jeff Christiansen of Superior Veterinary Surgical Solutions ... help with the pain of Lady’s arthritis. Dr Christiansen suggested that in conjunction with ...
(Date:5/24/2016)... ... May 24, 2016 , ... Media Cybernetics, global ... Media Cybernetics corporate branding reflects a results-driven revitalization for a company with a ... re-branding components include a crisp, refreshed logo and a new web presence. , ...
(Date:5/23/2016)... LONDON , May 23, 2016 ... Efficiency by 40% - Frontage Implement a Single Platform ... Quality, Compliance and Traceability Within the Bioanalytical lab Frontage ... the United States and China ... across its laboratory facilities. In addition to serving as the global ...
Breaking Biology Technology: