Yale Team Discover Alzheimer’s Pathway, Opportunity for Drug
A new discovery by a team of researchers at the Yale School of Medicine may open the door for an effective Alzheimer’s disease treatment. The researchers found a step in the neurological development of Alzheimer’s which appears to be easily blocked.
The researchers discovered a protein in mice with brain damage which mimics Alzheimer’s. When they disabled the protein the doctors say the mice actually had their memory restored. The finding could eventually lead to the creation of a drug to combat Alzheimer’s.
According to Dr. Stephen Strittmatter, professor of neurology and senior author of the study, published in the journal Neuron, says strings of amino acids called amyloid-beta peptides found at low levels in everyone’s body can “clump up in enormous balls that are called plaques,” which are “bigger than cells.”
These plaques are often found in high amounts in the brains of Alzheimer’s patients. They don’t form suddenly, however, and people destined to develop Alzheimer’s have these peptides come together in smaller bodies.
“Between the single (amyloid-beta peptide) molecule and these enormous aggregates (plaques), a few molecules come together … as one of the first steps in the disease process,” Strittmatter told The Register Citizen. “These smaller groups of cells are called amyloid-beta peptide oligomers, which are “thought to be toxic to neurons. The oligomers make neurons sick.”
The oligomers attach to proteins on the surface of a neuron and transmits a signal that impairs synapses. The researchers from Yale wanted to figure out what protein was carrying the signal. What they found was a protein embedded in the neuron cell’s membrane called metabotropic glutamate receptor 5, or mGluR5. The protein acts as the pathway between the inside and outside of the cell, allowing the oligomers to send destructive messages in. But, they also found it “is one that’s very easy to make drugs against.”
Using a drug similar to one being developed for Fragile X syndrome, mGluR5 was blocked in the brain-damaged mice. When it was blocked, the researchers found they could recover memory function and synapses.
The oligomers only show up in the blood of those who are destined to develop Alzheimer’s, but there is currently no test for them. There are many researchers already working on such a test, however.