Stem cell 'guide' may be key for targeting neural stem cell treatments

(2005-06-27)

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.

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Contact: Tom Vasich
tmvasich@uci.edu
949-824-6455
University of California - Irvine
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