Scientists reveal that protein agglomerations typical of neurodegenerative diseases dissociate with infrared laser irradiation
The agglomeration of proteins into structures called amyloid plaques is a common feature of many neurodegenerative diseases, including Alzheimer’s. Now, scientists reveal how resonance with an infrared laser when tuned to a specific frequency, causes amyloid fibrils to disintegrate from the inside out. Their findings open doors to novel therapeutic possibilities for amyloid plaque-related neurodegenerative diseases that have previously been incurable.
A notable characteristic of several neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, is the formation of harmful plaques that contain aggregates—also known as fibrils—of amyloid proteins.
After decades of research, getting rid of these plaques has remained a mystery and the treatment options available to patients with these disorders are limited and ineffective.
In recent years, rather than using drugs, some scientists have turned to alternative approaches, such as ultrasound, to destroy amyloid fibrils and halt the progression of Alzheimer’s disease.
Now, a research team led by Dr Takayasu Kawasaki (IR-FEL Research Center, Tokyo University of Science, Japan) and Dr Phuong H. Nguyen (Centre National de la Recherche Scientifique, France) has used novel methods to show how infrared-laser irradiation can destroy amyloid fibrils.
In their study, published in the Journal of Physical Chemistry B, the scientists present the results of laser experiments and molecular dynamics simulations. This two-pronged attack on the problem proved necessary because of the inherent limitations of each approach.
Dr Kawasaki said, “While laser experiments coupled with various microscopy methods can provide information about the morphology and structural evolution of amyloid fibrils after laser irradiation, these experiments have limited spatial and temporal resolutions, thus preventing a full understanding of the underlying molecular mechanisms.
“On the other hand, though this information can be obtained from molecular simulations, the laser intensity and irradiation time used in simulations are very different from those used in actual experiments. It is therefore important to determine whether the process of laser-induced fibril dissociation obtained through experiments and simulations is similar.”
The scientists used a portion of a yeast protein that is known to form amyloid fibrils. In their laser experiments, they tuned the frequency of an infrared laser beam to that of the “amide I band” of the fibril, creating resonance. Scanning electron microscopy images confirmed that the amyloid fibrils disassembled upon laser irradiation at the resonance frequency, and a combination of spectroscopy techniques revealed details about the final structure after fibril dissociation.
For the simulations, the researchers employed a technique that members of the team had previously developed, called “nonequilibrium molecular dynamics (NEMD) simulations.” Its results verified those of the experiment and clarified the amyloid dissociation process.
Through the simulations, the scientists observed that the process begins at the core of the fibril where the resonance breaks intermolecular hydrogen bonds and separates the proteins in the aggregate. The disruption to this structure then spreads outward to the extremities of the fibril.
Together, the experiment and simulation make a case for a potential novel treatment for neurodegenerative disorders.
Dr Kawasaki said: “In view of the inability of existing drugs to slow or reverse the cognitive impairment in Alzheimer’s disease, developing non-pharmaceutical approaches is very desirable. The ability to use infrared lasers to dissociate amyloid fibrils opens up a promising approach.”
The team’s long-term goal is to establish a framework combining laser experiments with NEMD simulations to study the process of fibril dissociation in even more detail, and new works are already underway.
