Using laser technology, researchers have found that peptides related to Alzheimer’s Disease move at dangerous speeds prior to clumping or forming the plaques that characterize the disease. Moreover, the scientists also identified strategies to keep the blocks that form the proteins moving at safe speeds.
The study, “Monomer Dynamics of Alzheimer Peptides and Kinetic Control of Early Aggregation in Alzheimer’s Disease,” was published in the journal ChemPsysChem.
Aggregation, or clustering, of proteins is the underlying cause of a large and growing number of degenerative and chronic diseases, such as Alzheimer’s disease (AD), a condition affects one in nine people 65 and older. AD is characterized by neuronal cell death and dementia apparently caused, at least in part, by aggregation of the amyloid beta peptide.
“Strings of 40 amino acids are the ones most commonly found in healthy individuals, but strings of 42 are much more likely to clump,” Lisa Lapidus, PhD, Michigan State University professor of physics and astronomy and study lead author, said in a press release. “We found that the peptides’ wiggle speeds, the step before aggregation, was five times slower for the longer strings, which leaves plenty of time to stick together rather than wiggle out of the way,” she said.
Lapidus’ team pioneered the use of lasers to analyze the speed at which proteins reconfigure before they aggregate and form plaques.
If protein’s reconfiguration is much faster or slower than the speed at which proteins bump into each other, aggregation is slow. However, if reconfiguration is the same speed at which proteins encounter, the aggregation activity is fast. Lapidus termed this mechanism as the “dangerous middle.”
“The dangerous middle is the speed in which clumping happens fastest,” Lapidus said. “But we were able to identify some ways that we can bump that speed into a safer zone.”
In their experiments, the team of researchers discovered that if they increased the levels of pH, the amino acids kept wiggling at fast and safe speeds. Also, when the researchers tested the effects of curcumin, they found it kept the peptide out of the dangerous middle.
Curcumin is an extract of the spice turmeric that has been shown to break down amyloid-beta plaques in lab-based in vitro studies. Turmeric is not easily absorbed and there is no real evidence that supports turmeric being used as a treatment for AD. However, curcumin could be a useful target for future investigations into potential treatments.
“Hence, this work may provide a novel approach toward therapeutic development for Alzheimer’s disease and, as shown herein, can be used to test whether a small-molecule inhibitor is able to arrest aggregation early on,” the researchers wrote.
The new study provides a potential for early detection of AD. When symptoms of AD start to appear, patients already have plaque aggregations in theirs brains. Monitoring amino acids and their wiggling speeds could warn clinicians long before the patient starts suffering from the disease.