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Researchers discover stem cell 'guide' that may be key for targeting neural
stem cell treatments

UCI study shows how new neurons created from adult stem cells are directed
to specific brain regions
Irvine, Calif. - UC Irvine School of Medicine researchers have discovered
how new neurons born from endogenous neural stem cells are sent to regions
of the brain where they can replace old and dying cells, a finding that
suggests how stem cell therapies can be specifically targeted to brain
regions affected by neurodegenerative diseases or by stroke.

Associate Professor Qun-Yong Zhou and graduate student Kwan L. Ng in the
UCI Department of Pharmacology have identified a protein that guides these
new neurons to a particular brain region. The protein, a small peptide
called prokineticin 2 (PK2), was found to play a key regulatory role for
the proper functional integration of these new neurons in the brain. A few
years ago, PK2 was shown by the same research group to be an important
regulator of circadian rhythms. The current study appears in the June 24
issue of the journal Science.

"One of the keys to developing promising new therapies for debilitating
neurodegenerative diseases lies in our understanding of how new neurons are
created and integrated into mature brain tissue," Zhou said. "This protein
is an attractive drug target for either boosting neuron-forming processes
or stem cell-based therapies for diseases like Alzheimer's and Parkinson's,
or for stroke and other brain injuries."

While all neurons are originally born and differentiated from their stem
cell progenitors during development, the adult brain maintains at least
some regions where neural stem cells create new neurons to replace old and
dying ones. One area is the subventricular zone of the lateral ventricles,
which are fluid-filled cavities in both brain hemispheres connected the
central canal of the spinal cord.

Zhou and his colleagues discovered how PK2 guides the migration of neurons
born from neural stem cells from the subventricular zone in the brain's
core through mature tissue to reach the olfactory bulb, the "smell" part of
the brain located above the sinus cavity. PK2 allows these new neurons to
settle into the proper areas of the olfactory bulb, thus permitting these
neurons to function normally.

"Our findings identify one of the first endogenous guidance molecules for
migrating neurons in the adult brain," Zhou said. "We are learning that
molecules, like PK2, which direct the movement of neurons are crucial for
neuronal replacement, and they demonstrate how adult stem cells might be
manipulated for this process."

PK2 accomplishes this task by working with its corresponding cell
receptors, which are part of the G protein-coupled receptor (GPCR) family.
GPCRs are proteins found in a cell's membrane and play a critical role in
transferring signals from outside of a cell to the molecular machinery
within the cell. GPCRs are the largest family of proteins that serve as
drug targets. It has been estimated that at least 40 percent of all
medicines on the market act on this family of receptors.


###
The research was supported by a UC Discovery Grant. In addition to Zhou and
Ng, co-authors on this study include Jia-Da Li, Michelle Y. Cheng, Frances
M. Leslie and Alex G. Lee of UCI's Department of Pharmacology.

About the University of California, Irvine: Celebrating 40 years of
innovation, the University of California, Irvine is a top-ranked public
university dedicated to research, scholarship and community service.
Founded in 1965, UCI is among the fastest-growing University of California
campuses, with more than 24,000 undergraduate and graduate students and
about 1,400 faculty members. The second-largest employer in dynamic Orange
County, UCI contributes an annual economic impact of $3 billion. For more
UCI news, visit http://www.today.uci.edu.

Contact: Tom Vasich
(949) 824-6455
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