Work has been carried out using latest-generation molecular
simulations
March 1, 2016
Source:
Source:
IMIM (Hospital del Mar Medical Research Institute)
Summary:
Using
latest-generation molecular simulations researchers have demonstrated that a
decrease in polyunsaturated lipids in neuronal membranes, as seen in
Parkinson's and Alzheimer's sufferers, directly affects the binding rate of
dopamine and adenosine receptors
A
study published in the journal Scientific Reportsfrom the Nature
group demonstrates, for the first time and using computational tools, that
polyunsaturated lipids can alter the binding rate of two types of receivers
involved in certain nervous system diseases. The work was led by members of the
Research Programme on Biomedical Informatics at the IMIM (Hospital del Mar
Medical Research Institute) and Pompeu Fabra University as well as researchers
from the University of Tampere (Finland), and also involved scientists from the
University of Barcelona.
Using
latest-generation molecular simulations, which are like "computational
microscopes," the researchers have demonstrated that a decrease in
polyunsaturated lipids in neuronal membranes, as seen in Parkinson's and
Alzheimer's sufferers, directly affects the binding rate of dopamine and
adenosine receptors. These are part of the family of receptors connected to the
G protein (GPCR), located in the cell membrane and responsible for transmitting
signals to within the cell. Until now, various studies have demonstrated that
lipid profiles in the brains of people with diseases like Alzheimer's and
Parkinson's are very different from those of healthy people. These studies
showed that the levels of a polyunsaturated fatty acid in neuronal membranes
are considerably lower in the brains of sufferers. The researchers believe that
this difference in the lipid composition of membranes could alter the way in
which certain proteins interact with each other, as in the case of the GPCR
receivers.
According
to Jana Selent, a researcher from the PharmacoInformatics group at the IMIM and
UPF "It has recently been discovered that the protein complex formed by
the binding of dopamine and adenosine receivers, two key GPCRs in diverse cerebral
processes, could be a potential therapeutic target in neurodegenerative
diseases like Parkinson's and Alzheimer's. Our study suggests that
polyunsaturated lipids like DHA are able to modulate the speed at which this
protein complex forms, and that could in turn affect its function."
The
researchers used latest-generation molecular simulation techniques that allow
them to observe, almost at the atomic level, biological dynamics that cannot be
described with experimental techniques. Until relatively recently, it was not
possible to conduct molecular simulations of this magnitude. However, this
field has undergone an important evolution over the past few years, thanks to
new breakthroughs in both hardware and software. "In this way, taking
advantage of the latest technology in the field of biocomputation, we have been
able to simulate the binding dynamics of these two receptors in distinct lipid
membranes, an important biological scenario for nervous system diseases,"
explains Ramon Guixà González, a researcher currently affiliated with the
Charité Hospital in Berlin and co-author of this study.
These
results will enable, in the future, new therapeutic pathways to be initiated
for regulating the binding of these receivers, either through the lipid composition
of the membrane or by designing new lipids that have a modulating effect on
this binding rate. It will also facilitate the study of other similar scenarios
where specific membrane lipids are able to modulate the behaviour of other
important receivers, at a clinical level. Even so, the researchers say the most
important short-term challenge is looking at the real impact of reducing or
increasing the formation speed of this protein complex on the cell function
where it is expressed.
Story
Source:
The above
post is reprinted from materials provided
by IMIM (Hospital del Mar Medical
Research Institute). Note: Materials may be edited for
content and length.
Journal
Reference:
Ramon
Guixà-González, Matti Javanainen, Maricel Gómez-Soler, Begoña Cordobilla, Joan
Carles Domingo, Ferran Sanz, Manuel Pastor, Francisco Ciruela, Hector
Martinez-Seara, Jana Selent. Membrane omega-3 fatty acids modulate the
oligomerisation kinetics of adenosine A2A and dopamine D2 receptors. Scientific
Reports, 2016; 6: 19839 DOI: 10.1038/srep19839
https://www.sciencedaily.com/releases/2016/03/160301130915.htm?
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