Flinders: In
a world first, neuroscientists at Flinders University have identified a
series of chemical tools that can either increase or inhibit the
release of neurotransmitters by neurons, the cells of the brain. While not yet applied to a specific disease, the discovery has a wide
range of potential pharmaceutical applications in neurological
conditions ranging from schizophrenia to depression. A team led by Pr Damien Keating has
published a paper on the action of a protein called dynamin in the
latest issue of the prestigious journal Molecular Psychiatry.
Vesicles – small spherical bodies within cells – contain active
chemicals that can include neurotransmitters or hormones. Associate
Professor Keating’s research is concerned with the process which sees
vesicles move to the surface of a cell before opening a pore that allows
the release of these active chemicals. The opening is then reversed and
the vesicle moves back down into the cell to be reused.
Associate Professor Keating’s current research focuses on a protein
named dynamin, already known to drive the process of resealing and
recycling these vesicles. The breakthrough discovery has established
that dynamin is also involved earlier in the process, and is a master
regulator of the amount of neurotransmitter released from each vesicle.
Associate Professor Keating said the opening and closing of fusion
pores – the vesicle’s temporary door through the cell wall – is dynamic,
with differences in the size and duration of the opening controlling
the amount of active chemical that is released.
Variations in levels of dynamin directly affect that process, and it
is a process that underpins all our neuronal communication and hormone
release, Associate Professor Keating says.
“If we activate dynamin, more is released by the vesicle; if we
inhibit it, less is released,” he said. “This is fundamental new
knowledge about a process that is essential to life in all organisms.”
Associate Professor Keating is collaborating with medicinal chemists
and cell biologists in Sydney and Newcastle to further develop and
refine these dynamin-based drugs.
“This research is novel in terms of identifying what this protein
does – it plays a major new role that we did not know about – and it is
novel in terms of the use of these drugs and their potential
application,” he said.
“There is a lot work to be done to see how these drugs can be
applied, but any neurological or metabolic disorder where neuronal or
hormone signalling is a factor is a possible target, and any drug that
can affect how much neurotransmitter or hormone is available has
potential for usage in treatment,” he said.