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:
- Alzheimer's drug could reduce damaging brain plaques by 70%, animal study suggestson March 5, 2021 at 4:39 am
An Alzheimer's drug has shown promise in animals. The memory-robbing disease has no cure, with treatments aiming to temporarily ease symptoms. Alzheimer's is thought to come about when proteins ...
- Alzheimer’s Disease: Drug Prevents Amyloid Plaques in Animal Modelson March 3, 2021 at 2:32 am
In a new study, researchers report that they have identified a new drug that could prevent Alzheimer's disease by modulating, rather than inhibiting, a key enzyme involved in the formation of amyloid ...
- New drug shows potential as prophylactic for Alzheimer’s diseaseon March 2, 2021 at 6:20 pm
In pre-clinical studies, a novel treatment decreased plaque formation, meaning it could be used to prevent Alzheimer's disease.
- Novel drug prevents amyloid plaques, a hallmark of Alzheimer's diseaseon March 2, 2021 at 5:13 pm
Researchers have identified a new drug that could prevent AD by modulating, rather than inhibiting, a key enzyme involved in forming amyloid plaques.
- New Drug Prevents Buildup of Brain Plaques Responsible for Alzheimer’son March 2, 2021 at 10:10 am
Scientists have developed a new drug that modulates a key enzyme responsible for forming the amyloid plaques linked to the onset of Alzheimer’s disease.
Go deeper with Google Headlines on:
Go deeper with Bing News on:
- Scientists Want to Destroy Zombie Satellites With Lasers. What Could Go Wrong?on March 3, 2021 at 5:44 am
Otherwise, blasting the wrong parts can create clouds of small debris. Just one problem: having a laser to remove space junk also means having a laser that could destroy active satellites.
- Photocrosslinking and photopatterning of magneto-optical nanocomposite sol–gel thin film under deep-UV irradiationon March 3, 2021 at 5:04 am
This paper is aimed at investigating the process of photocrosslinking under Deep-UV irradiation of nanocomposite thin films doped with cobalt ferrite magnetic nanoparticles (MNPs). This material is ...
- Scientists Want to Destroy Zombie Satellites With Lasers. What Could Go Wrong?on March 2, 2021 at 2:31 pm
The right lasers could melt space junk, like satellites, into plasma.The secret is to concentrate on space junk parts that we can reduce to nothing. Otherwise, blasting the wrong parts can create ...
- Hamamatsu launches laser thermal processor for quenchingon March 2, 2021 at 11:20 am
Hamamatsu Photonics has developed new laser thermal processing equipment for laser quenching that combines a direct diode laser, based on the firm’s own diode technology, with a ...
- Keloid Treatment Market Forecast to 2027 – COVID-19 Impact and Global Analysis By treatment type and End User, and Geographyon March 2, 2021 at 8:56 am
According to the latest market report published by FMI titled ‘Keloid Treatment Market: Global Industry Analysis (2012-2016) and Opportunity Assessment (2017-2027),’the global keloid treatment market ...