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H E A L H A N D S O C I E Y
R E S E A R C H @ H K U S
HKUST neuroscientists have made significant advances
in understanding synapse and protein trafficking involving
kinases C (PICK1), thrombospondin and neuroligin, as
well as G-protein-coupled receptors (GPCRs), among
others. These are some of the many proteins responsible
for changes in neuron communication and information
processing that can lead to neurodegeneration.
PICK1 Regulation
Prof Jun Xia, Professor of Life
Science, and his team have
looked into proteins that are
important for synapse formation
and function, with advances
on thrombospondin and
neuroligin published in
Nature
Neuroscience
. “Each cell has about 25,000 proteins. Several
hundreds are thought to be implicated in neurodegeneration.
But we know very little how these proteins act individually or
collectively in contributing to neurodegenerative diseases,”
said Prof Xia.
Their studies found that thrombospondin can bind to
neuroligin to promote synapse formation. More notably they
investigated the regulation of protein trafficking by the PICK1
protein, and how abnormal protein trafficking can contribute
to neuron degeneration. Without PICK1 synapse strength
cannot be changed, affecting brain plasticity that is vital for
normal cognitive functions, including learning and memory.
G-protein
Meanwhile, Prof Yung Hou
Wong, Chair Professor of Life
Science, and Director of HKUST
Biotechnology Research
Institute, is studying the
molecular mechanisms of how
a cell responds to extracellular
signals, such as neurotransmitters and hormones. This
often involves G-protein-coupled receptors (GPCRs) that
use G-proteins to regulate cellular communications in
the brain and other organs. They are fundamental to cell
communication and malfunctioning of either G-proteins
or their receptors may lead to diseases. For example, a
defective dopamine receptor system causes Parkinson’s
disease.
Prof Wong and his team have also screened and identified
molecules from traditional Chinese medicinal herbs that work
on melatonin receptors, GPCRs that regulate our biological
clock. The new drug candidates promise to be more useful
than current drugs in treating sleep disorders with fewer side
effects, and may also have implications for neurodegenerative
diseases, since clinical research shows that patients with
these diseases who sleep better have a better prognosis.
Melatonin receptors have also been linked with mechanisms
that can protect neurons.
Comprehending Parkinson’s
Parkinson’s disease is the second most
common neurodegenerative disorder
after Alzheimer’s disease and the major
risk factor for the disease is aging. People
with family history of this disease have an
increased risk of getting the disorder.
Prof Kenny K Chung has identified im-
portant molecular mechanisms of neuro-
degeneration, focused on familial Parkin-
son’s disease – the form that is caused by
geneticmutation(s). He has beenworking
on genes involved in familial cases focus-
ing on the gene known as parkin, its func-
tions in relation to mitochondria, and the
neural pathways affected during the dis-
ease. Prof Chung and his team have found
one of the redox signaling pathways that
can affect the function of parkin, and later
on other protective genes. This is through
nitric oxide, an important signaling
molecule in the brain. Once this pathway
is understood, one might be able to find
ways of pathway modulation for potential
therapy for the disease.
Hunting Huntington’s
Prof Hyokeun Park is investigating the
roles of brain-derived neurotrophic factor
(BDNF). Produced in cell bodies in neu-
rons and transported to synapses, BDNF
is important for maintaining synapses
in neurons. Research has found that
there is a lack of BDNF in the striatum in
Huntington’s disease patients. Prof Park
has observed that there are differences
in transport and their release of BDNF-
containing vesicles in Huntington’s dis-
ease mice compared with normal mice.
“BDNF is very important for neuron sur-
vival. If we can increase the BDNF level
in the striatum in Huntington’s disease
system, it may help slow down the pro-
gression of Huntington’s disease,” he said.
PROF KENNY K CHUNG
Associate Professor of
Life Science
PROF HYOKEUN PARK
Assistant Professor of
Life Science
The Power of Proteins
Mitochondrial
dysfunction is
one of the major
contributors to
Parkinson’s disease.
Left: Dysfunctional
mitochondria
in a model of
Parkinson’s disease.
Far left: Healthy
mitochondria.
