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Researchers find possible solutions to reverse Alzheimer's Disease impact
Overview
University of North Carolina at Chapel Hill researchers have developed a new drug delivery platform that harnesses helical amyloid fibers designed to untwist and release drugs in response to body temperatures.
A new research paper published on Jan. 26 in Nature Communications reveals groundbreaking structural details into how diseases form much like Alzheimer's disease. With this knowledge, the group may have uncovered a unique mechanism to reverse both the deposits and their impact on those suffering from these conditions.
The Invedtgation
• UNC-Chapel Hill researcher Ronit Freeman is leading a research group with investigators from the Lynn lab at Emory University looked at the core beta amyloid-42 peptide, the key portion driving amyloid plaque assembly and deposits in the brains of patients with Alzheimer's disease.
• By creating synthetic variations of the peptide in the lab, they were able to discover how to control the way that these molecules assemble and twist.
Power of Amyloid Materials
• "The ability of these amyloid materials to be untwisted and degraded highlights potential for treatments modifying and subsequently reversing plaques found in Alzheimer’s, and other neurodegenerative diseases," said Freeman.
• "We know that the direction of the amyloid fibril twists is associated with different disease progression states. Imagine that by a simple treatment, we could modify amyloids to change their shape and disappear - this is what our discovery might enable us to do in the future."
How Peptides Work
• Using advanced spectroscopic techniques, the researchers probed how individual peptides interact, revealing information about assembly rates, distances between peptides, peptide alignment, and importantly the direction of twist.
• High-resolution electron and fluorescent microscopy were used to characterize the morphology of the materials at different temperatures.
Peptide Structure and Its Work
• The investigators identified that the N-terminal domain of the peptide is important for programming the shape of the assembly such as tubes, ribbons, or fibers, while C-terminal modifications direct either a left- or right-handed twist within the material.
• Using these design rules, a series of peptides were tuned to switch on-demand between left-handed and right-handed twisted ribbons in response to changing temperatures.
• This twist inversion then renders the material susceptible to degradation by natural proteins, a desirable feature for materials used as delivery vehicles.
