Nama : Nusa Chandra
NIM :
1177000077
Kelas : Psikologi 2B
Matkul : B.
Inggris
“Brain protein crucial to recovery from stroke”
Date : February 11, 2019
Source : University of Pittsburgh
Summary :
Researchers have identified a brain protein at the root of how the brain
recovers from stroke. The finding offers a
promising avenue for developing therapies that could work even when given
beyond the first few hours after a stroke.
Every 40 seconds, someone in the United
States suffers a stroke and available therapies, such as clot busting drugs or
clot removal devices, are focused on limiting the extent of brain damage. Now,
research from the University of Pittsburgh School of Medicine and the VA
Pittsburgh Healthcare System shows that a brain protein called UCHL1 may be
critical to how nerve cells repair themselves after stroke damage. The
research, conducted in animal models, could aid in the development of therapies
that enhance stroke recovery by improving the underlying biological repair
process."Even though traditional stroke therapies are very effective when
available, the treatment must be started in the first hours after a stroke and
most patients are not able to get these treatments. So there is a clear need
for new approaches that can improve recovery days after a patient experiences a
stroke," said co-senior author Steven Graham, M.D., Ph.D., professor of
neurology at Pitt's School of Medicine, and associate chief of staff for
research at VA Pittsburgh. "We think we have identified a protein that is
at the root of how the brain recovers from stroke, making it an attractive
target for developing drugs that help improve recovery."
UCHL1 is an enzyme that is highly active in
the brain and plays a role in clearing away abnormal proteins. Mutations in the
gene coding for UCHL1 have been thought to cause motor function deficits in
humans. Previous research from Graham's lab had provided some hints as to
UCHL1's function, showing that cyclopentenone prostaglandins (CyPgs) -- fatty
acid molecules -- released in nerve cells after a stroke bind to UCHL1 and
impair its function.
Graham teamed up with Feng Zhang, Ph.D., an
assistant professor of neurology at Pitt's School of Medicine and a co-senior
author on the current study published in the Proceedings of the National
Academy of Sciences, to tease out the exact role of UCHL1 in stroke and to
determine if it could be a viable drug target.
The researchers created a mouse model in
which they inserted an altered version of the UCHL1 gene that was resistant to
the effects of the CyPgs. They then surgically modelled the effect of a stroke
in both genetically engineered and normal mice to compare how the nerve cells
recovered.
Preventing CyPgs from inhibiting UCHL1
decreased the amount of injury to the axons after stroke when compared to
normal mice. Axons -- the long cables projecting outward from the center of the
nerve cell -- are needed to carry electrical signals and connect to other
neurons and make up the bulk of the 'white matter' in the brain.
Further experiments showed that keeping
UCHL1 active after a stroke helped preserve the function of neurons and brain
tissue by activating cellular repair mechanisms that quickly cleaned up damaged
proteins, preventing further nerve cell loss. The mice with the resistant form
of UCHL1 also had improved recovery of waking, balance and other motor
functions.
"While most stroke therapies focus on
preventing neuronal death, preserving axonal integrity and decreasing white
matter injury could be equally important for improved recovery," said
Graham, who also is a neurologist at the UPMC Stroke Institute. "UCHL1 is
a central player in that process."
Graham and his colleagues are now engaged
in efforts to identify new drugs that could prevent CyPgs from binding to UCHL1
or to replace damaged UCHL1 proteins with a derivative that can be given
intravenously.
Story Source : Materials provided by
University of Pittsburgh. Note: Content may be edited for style and length.
Journal Reference : Hao Liu, Nadya
Povysheva, Marie E. Rose, Zhiping Mi, Joseph S. Banton, Wenjin Li, Fenghua
Chen, Daniel P. Reay, Germán Barrionuevo, Feng Zhang, Steven H. Graham. Role of
UCHL1 in axonal injury and functional recovery after cerebral ischemia.
Proceedings of the National Academy of Sciences, 2019; 201821282 DOI:
10.1073/pnas.1821282116