Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING LLC
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC

Experimental Drug Restores Communication Between Synapses in Mouse Alzheimer's Disease Model

By BiotechDaily International staff writers
Posted on 02 Jul 2013
Image: Photomicrograph of nerve cell during an electrical recording (left), fluorescently labeled nerve cell (right), (Photo courtesy of Sanford-Burnham Medical Research Institute).
Image: Photomicrograph of nerve cell during an electrical recording (left), fluorescently labeled nerve cell (right), (Photo courtesy of Sanford-Burnham Medical Research Institute).
A new drug assembled from two [US] Food and Drugs Administration (FDA)-approved compounds completely restored amyloid-beta-induced synaptic loss in an animal model of Alzheimer's disease (AD), providing hope for rapid development of a drug that would benefit patients already displaying symptoms of the disease.

While the breakdown of communications between synapses characterizes cognitive decline in AD, the mechanism of synaptic damage remains incompletely understood.

Investigators at Sanford-Burnham Medical Research Institute (La Jolla, CA, USA) recently described a pathway for synaptic damage whereby amyloid-beta1–42 peptide (A-beta1–42) released, via stimulation of alpha7 nicotinic receptors, toxic amounts of glutamate from astrocytes, in turn activating extrasynaptic NMDA (N-methyl-D-aspartate) -type glutamate receptors (eNMDARs).

They noted that the FDA-approved drug memantine offered some limited beneficial effect in severe cases of AD. The drug belongs to the NMDA receptor antagonist class of drugs, which reduce certain types of brain activity by binding to NMDA receptors on brain cells and blocking the activity of the neurotransmitter glutamate. At normal levels, glutamate aids in memory and learning, but if levels are too high, glutamate appears to over stimulate nerve cells, killing them through excitotoxicity.

Memantine has been associated with a moderate decrease in clinical deterioration with only a small positive effect on cognition, mood, behavior, and the ability to perform daily activities in moderate to severe Alzheimer's disease. There does not appear to be any benefit in mild disease.

The investigators reported in the June 17, 2013, online edition of the journal Proceedings of the National Academy of Sciences of the United States of America (PNAS) that when memantine was modified by the addition of a fragment of the FDA-approved drug nitroglycerine, the new drug—NitroMemantine—restored lost synapses in an AD animal model. The memantine component of the drug directed it to synapses where the nitroglycerine fragment inhibited glutamate release.

“We show in this paper that memantine’s ability to protect synapses is limited,” said senior author Dr. Stuart A. Lipton, professor of neuroscience, aging, and stem cell research at Sanford-Burnham Medical Research Institute, “but NitroMemantine brings the number of synapses all the way back to normal within a few months of treatment in mouse models of Alzheimer’s disease. In fact, the new drug really starts to work within hours.”

“These findings actually mean that you might be able to intercede not only early but also a bit later,” said Dr. Lipton, “and that means that an Alzheimer’s patient may be able to have synaptic connections restored even with plaques and tangles already in his or her brain. I am now optimistic that NitroMemantine will be effective as we advance to human trials, bringing new hope to both early and later-stage Alzheimer’s patients.”

Related Links:
Sanford-Burnham Medical Research Institute



Channels

Genomics/Proteomics

view channel
Image: In mice, mitochondria (green) in healthy (left) and Mfn1-deficient heart muscle cells (center) are organized in a linear arrangement, but the organelles are enlarged and disorganized in Mfn2-deficient cells (right) (Photo courtesy of the Rockefeller Press).

Cell Biologists Find That Certain Mitochondrial Diseases Stem from Coenzyme Q10 Depletion

A team of German cell biologists has linked the development of certain mitochondrial-linked diseases to depletion of the organelles' pool of coenzyme Q10 brought about by mutation in the MFN2 gene, which... Read more

Biochemistry

view channel

Possible New Target Found for Treating Brain Inflammation

Scientists have identified an enzyme that produces a class of inflammatory lipid molecules in the brain. Abnormally high levels of these molecules appear to cause a rare inherited eurodegenerative disorder, and that disorder now may be treatable if researchers can develop suitable drug candidates that suppress this enzyme.... Read more

Lab Technologies

view channel
Image: The FLUOVIEW FVMPE-RS Gantry microscope (Photo courtesy of Olympus).

New Multiphoton Laser Scanning Microscope Configurations Expand Research Potential

Two new configurations of a state-of-the-art multiphoton laser scanning microscope extend the usefulness of the instrument for examining rapidly occurring biological events and for obtaining images from... Read more

Business

view channel

Roche Acquires Signature Diagnostics to Advance Translational Research

Roche (Basel, Switzerland) will advance translational research for next generation sequencing (NGS) diagnostics by leveraging the unique expertise of Signature Diagnostics AG (Potsdam, Germany) in biobanks and development of novel NGS diagnostic assays. Signature Diagnostics is a privately held translational oncology... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.