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Researchers at McGill University have found that sodium – the main
chemical component in table salt – is a unique “on/off” switch for a
major neurotransmitter receptor in the brain. This receptor, known as
the kainate receptor, is fundamental for normal brain function and is
implicated in numerous diseases, such as epilepsy and neuropathic pain.
Prof. Derek Bowie and his laboratory in McGill’s Department of
Pharmacology and Therapeutics, worked with University of Oxford
researchers to make the discovery. By offering a different view of how
the brain transmits information, their research highlights a new target
for drug development. The findings are published in the journal Nature Structural & Molecular Biology.
Balancing kainate receptor activity is the key to maintaining normal
brain function. For example, in epilepsy, kainate activity is thought to
be excessive. Thus, drugs which would shut down this activity are
expected to be beneficial.
“It has been assumed for decades that the “on/off” switch for all
brain receptors lies where the neurotransmitter binds,” says Prof.
Bowie, who also holds a Canada Research Chair in Receptor Pharmacology.
“However, we found a completely separate site that binds individual
atoms of sodium and controls when kainate receptors get turned on and
off.”
The sodium switch is unique to kainate receptors, which means that
drugs designed to stimulate this switch, should not act elsewhere in the
brain. This would be a major step forward, since drugs often affect
many locations, in addition to those they were intended to act on,
producing negative side-effects as a result. These so called “off-target
effects” for drugs represent one of the greatest challenges facing
modern medicine.
“Now that we know how to stimulate kainate receptors, we should be
able to design drugs to essentially switch them off,” says Dr. Bowie.
Dr. Philip Biggin’s lab at Oxford University used computer
simulations to predict how the presence or absence of sodium would
affect the kainate receptor.
The research was made possible in part thanks to a grant from The
Brain@McGill, a partnership between Oxford University, Neuroscience
Center Zurich (ZNZ) and McGill aimed at enhancing research
collaborations in neuroscience.
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