Green Glow Illuminates Possible Alzheimer's Breakthrough
Discovery of a protein that dissolves amyloid-beta 42, which is believed to form clumps that lead to the onset and progression of Alzheimer's, could eventually lead to treatments that could reverse the disease. A potential cure is years away, however. Scientists need to see if their lab findings are confirmed in experiments with organisms. A fruit fly study is set for this fall.
08/06/09 2:26 PM PT
Researchers at two Southern California schools may have achieved a breakthrough in the search for chemicals that can slow -- or even reverse -- the progression of Alzheimer's disease and possibly even diabetes.
Assistant professor of biochemistry David Moffet and Luiza Nogaj, a professor at MSM, lead a team of undergraduates who recently discovered three substances that slow development of a key aspect of Alzheimer's.
Even better, one of these proteins -- peptide 2 -- actually reverses the "clumping" that scientists say is associated with its onset and progression.
"Nobody knows for sure exactly what causes Alzheimer's, but the 'amyloid hypothesis' holds that a brain protein known as amyloid-beta 42, or AB42, appears to form aggregates, or 'clumps,' and these aggregates lead to Alzheimer's disease," Moffet told TechNewsWorld.
"We thought that if you could prevent that aggregation, you might be able to slow or even stop Alzheimer's," he added.
Thus began the search for a protein that could stop the clumping, and perhaps someday provide relief for a disease that afflicts more than 5.3 million people in the United States alone.
The Shine of Success
The team began with a huge database of proteins. Students tested protein after protein with a technique involving green fluorescence. If the protein being tested prevented or slowed clumping, then the chemicals would have time to fluoresce.
No glow would indicate clumping had occurred so quickly that the chemicals didn't have time to undergo fluorescence.
By the time they finished testing thousands of chemicals, the researchers had found three that slowed the clumping, indicating they might delay the onset or slow the progression of Alzheimer's disease.
One of them, peptide 2, actually attacks AB42, dissolving it. The test mixture gives off a distinct glow, one that could signal success in the struggle against the malady.
"If it works as well in living organisms as it does in the lab, we might be able to actually reverse Alzheimer's disease someday," said Moffet.
"That's the next step, and this fall, we'll actually test peptide 2 on living organisms," he said.
That's when biology professor Cathy McElwain will test peptide 2 on fruit flies to see if it prevents the disease in the insects. In case you're wondering how researchers will be able to tell if fruit flies get Alzheimer's, Moffet explained that fly sufferers live about half as long as their healthy counterparts, and they lose the ability to climb the walls of their enclosures shortly before they die.
While cures resulting from such research are years away, at best, Moffet said the green fluorescence technique -- developed by Michael Hecht, a Princeton University professor -- may offer payoffs in the fight against other diseases in which clumping plays a role.
"We have another project under way to see if we can do a similar thing for diabetes," said Moffet. "There's evidence that a protein called 'IAPP' causes the same kind of aggregation in the pancreas, causing diabetes. We're trying to see if we can find chemicals that inhibit or reverse the damage associated with IAPP."
"Inhibition of ABeta42 Aggregation Using Peptides Selected from Combinatorial Libraries," a paper summarizing the Alzheimer's research, is scheduled for publication in the Journal of Peptide Science in August.