Misfolded proteins thought to play a critical role in the progress of various neurodegenerative conditions could be prevented from forming toxic plaques with the injection of a specially designed nanomaterial.
Developed by an international team of researchers, the tiny particles with both fat- and water-loving properties were shown to trap misbehaving amyloid beta proteins before they could clump together, protecting tissue against damage thought to be responsible for Alzheimer’s disease.
“In many of these diseases, proteins lose their functional folded structure and aggregate to make destructive fibers that enter neurons and are highly toxic to them,” says Northwestern University materials scientist Samuel Stupp.
“By trapping the misfolded proteins, our treatment inhibits the formation of those fibers at an early stage. Early stage, short amyloid fibers, which penetrate neurons, are believed to be the most toxic structures. With further work, we think this could significantly delay progression of the disease.”
The treatment is based on a compounds known as peptide amphiphile, which mix just as readily with lipids as they do water. These molecules are already used in other drugs, including semaglutide (better known as Ozempic).
There was another secret ingredient here though: trehalose. This naturally occurring sugar has previously been shown to be effective at making sure proteins don’t start misfolding, which is the abnormal behavior that then leads to dangerous protein clumps.
“Trehalose is naturally occurring in plants, fungi, and insects,” says organic chemist Zijun Gao, also from Northwestern University. “It protects them from changing temperatures, especially dehydration and freezing.”
“Others have discovered trehalose can protect many biological macromolecules, including proteins. So, we wanted to see if we could use it to stabilize misfolded proteins.”
Something special happens when peptide amphiphiles are combined with trehalose, the team found. The sugar makes the molecular structure less stable and solid, encouraging reactions with proteins such as amyloid beta.
As a result of the change in structure, amyloid beta proteins find their way into the sugar-enhanced peptide amphiphiles framework, where they can’t do any harm. This essentially traps potentially dangerous proteins, reducing the risk to neurons in what the researchers refer to as a “clean-up crew” for misfolded proteins.
This approach works a little differently to what we’ve previously seen in terms of tackling toxic proteins, because it aims to destabilize them at an earlier stage – before the amyloid fibers become well-established and more difficult to shift.
Research remains in its early stages, with studies needing to be carried out to measure the impact these sugar-coated molecules might have on the bodies of people with neurodegenerative conditions.
What we do know for certain is that innovative treatments for Alzheimer’s and other similar conditions are very much needed. Estimates suggest 10 million new diagnoses of dementia are made across the world each year, and that figure is expected to keep climbing as the global population continues to get older.
“Our study highlights the exciting potential of molecularly engineered nanomaterials to address the root causes of neurodegenerative diseases,” says Stupp.
The research has been published in the Journal of the American Chemical Society.
