Colored light micrograph of brain tissue from an Alzheimer’s disease sufferer. Both of the classic pathological features of this disease are seen here. At lower right is a large plaque (pink/blue) containing the abnormal protein amyloid. Also seen are several neurofibrillary tangles (smaller blue areas), thickened parts of the cytoplasm of nerve cells. Both of these abnormalities disrupt the normal working of the brain. The symptoms of Alzheimer’s Disease include memory loss (particularly of recent events), disorientation and mood changes. Death occurs after several years of decline, and there is no cure. Magnification: x50 at 6x7cm size.
(Image/Simon Fraser, Science Source)
The power of simulations combined with experiments reveals why 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, through experiments and simulations, how resonance with an infrared laser, when it is 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 thus far 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. Unfortunately, even after decades of research, getting rid of these plaques has remained a herculean challenge. Thus, the treatment options available to patients with these disorders are limited and not very effective.
In recent years, instead of going down the chemical route 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), including other researchers from the Aichi Synchrotron Radiation Center and the Synchrotron Radiation Research Center, Nagoya University, Japan, has used novel methods to show how infrared-laser irradiation can destroy amyloid fibrils.
In their study,published in Journal of Physical Chemistry B, the scientists present the results of laser experiments and molecular dynamics simulations. This two-pronged attack on the problem was necessary because of the inherent limitations of each approach, as Dr Kawasaki explains, “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 on its own. 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 a few members of the current team had previously developed, called “nonequilibrium molecular dynamics (NEMD) simulations.” Its results corroborated those of the experiment and additionally clarified the entire amyloid dissociation process down to very specific details. Through the simulations, the scientists observed that the process begins at the core of the fibril where the resonance breaks intermolecular hydrogen bonds and thus 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 good case for a novel treatment possibility for neurodegenerative disorders. Dr Kawasaki remarks, “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. All these efforts will hopefully light a beacon of hope for those dealing with Alzheimer’s or other neurodegenerative diseases.
The Latest Updates from Bing News & Google News
Go deeper with Bing News on:
- Study of Seniors Shows Tau Protein Buildup Key to Alzheimer’son February 24, 2021 at 9:09 am
Researchers may have uncovered a key reason some people remain sharp as a tack into their 80s and 90s: Their brains resist the buildup of certain proteins that mark Alzheimer’s disease. The study ...
- Why Some 'Super Ager' Folks Keep Minds Dementia-Freeon February 23, 2021 at 10:57 am
The study focused on what scientists have dubbed "super agers" -- a select group of older folks who have the memory performance of people decades younger. Compared with older people who had average ...
- Why some 'super ager' folks keep their minds dementia-freeon February 23, 2021 at 10:21 am
(HealthDay)—Researchers may have uncovered a key reason some people remain sharp as a tack into their 80s and 90s: Their brains resist the buildup of certain proteins that mark Alzheimer's disease.
- Melanocortin receptor activation alleviates amyloid pathology and glial reactivity in an Alzheimer’s disease transgenic mouse modelon February 23, 2021 at 5:44 am
Alzheimer’s disease (AD) is among the most common neurodegenerative disorders and is characterized by the progressive deterioration of memory and cognitive functions. The major pathological hallmarks ...
- Brain network analysis reveals that amyloidopathy affects comorbid cognitive dysfunction in older adults with depression | Scientific Reportson February 22, 2021 at 8:22 am
Late-life depression (LLD) may increase the risk of Alzheimer’s dementia (AD). While amyloidopathy accelerates AD progression, its role in such patients has not yet been elucidated. We hypothesized ...
Go deeper with Google Headlines on:
Go deeper with Bing News on:
- Study Investigates Wave Property of Atomic Nuclei Motion with Highest Accuracyon February 19, 2021 at 8:18 am
Under the guidance of Professor Stephan Schiller, PhD, from Heinrich Heine University Düsseldorf (HHU), a working group has utilized an innovative, high-precision laser spectroscopic experiment to ...
- Er: YAG laser improves gingival esthetics by removing Metal tattoo, Study sayson February 18, 2021 at 4:30 pm
According to recent research, investigators have found out that a minimally invasive therapy for metal tattoo removal that involved the Er: YAG laser is effective and safe, is associated ...
- Glowing nanocrystals enable 3D X-ray imagingon February 17, 2021 at 4:16 pm
Persistently luminescent nanocrystals have been used to make flexible X-ray detectors that produce better images of 3D objects than do the flat-panel detectors currently widely used in radiography.
- Laser Cleaning Machine Market to Rise with Impressive CAGR | Players – IPG Photonics, Hans Laser.on February 15, 2021 at 10:19 pm
Laser Cleaning Machine size was USD 580.8million is the year of 2019 and is expected to reach 720.9 Million is 2027 ...
- Laser-induced layers peeling of sputtering coatings at 1064 nm wavelengthon February 12, 2021 at 3:08 am
Large-scale layers peeling after the laser irradiation of dual ion beam sputtering coatings is discovered and a model is established to explain it. The laser damage morphologies relate to the laser ...