New study shows how infrared lasers destroy harmful protein aggregates
in Alzheimer's

Date:
August 4, 2020
Source:
Tokyo University of Science
Summary:
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.



FULL STORY ==========================================================================
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.


========================================================================== Story Source: Materials provided by Tokyo_University_of_Science. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Takayasu Kawasaki, Viet Hoang Man, Yasunobu Sugimoto, Nobuyuki
Sugiyama,
Hiroko Yamamoto, Koichi Tsukiyama, Junmei Wang, Philippe
Derreumaux, Phuong H. Nguyen. Infrared Laser-Induced Amyloid
Fibril Dissociation: A Joint Experimental/Theoretical Study on
the GNNQQNY Peptide. The Journal of Physical Chemistry B, 2020;
124 (29): 6266 DOI: 10.1021/ acs.jpcb.0c05385 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200804111501.htm

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