Easy way found to convert stem cells into neurons, could heal Alzheimer's

First Posted: Jan 14, 2013 11:43 AM EST
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It is possible to convert stem cells into functional neurons by repressing a single protein, scientists in the U.S. and China found, which could allow for huge progress in the treatment of neurodegenerative diseases like Huntington's, Parkinson's and Alzheimer's.

The targeted stem cells are ordinary fibroblasts, which form the connective tissue and are the most common type of cell - as pluripotent stem cells, their natural role is to fill in for general repairs in various parts of the body.

The scientists employed a radically new way to manipulate the stem cells, focussing on the  surprising and singular role of PTB, an RNA-binding protein long known for its role in the regulation of alternative RNA splicing, as well as how the regulation of the protein itself is regulated.

The team found with in vitro experiments that the concentration of PTB is chemically influenced in feedback loops by so-called microRNA molecules, a class of small molecules that modulate the expression of up to 60 percent of genes in humans. Approximately 800 different miRNAs, which have been identified and characterized to various degrees, are currently known.

The scientists at University of California, San Diego School of Medicine and Wuhan University in China report that one of these miRNAs, known as miR-124, specifically modulates levels of PTB during brain development. They observed the effect that when diverse cell types were depleted of PTB, they became neuronal-like cells or even functional neurons - an unexpected effect.

Lead researcher Xiang-Dong Fu, PhD, professor of cellular and molecular medicine at UC San Diego, said that while it's not known which neuronal signal or signals trigger the observed loop, the mechanism should already allow far reaching possibilities for scientists seeking new treatments for an array of neurodegenerative diseases, with the existing ability to artificially manipulate PTB levels in cells, inducing them to become neurons.

Current prognosis estimates that over a lifetime, one in four Americans will suffer from a neurodegenerative disease, from Alzheimer's and Parkinson's to multiple sclerosis and amyotrophic lateral sclerosis (Lou Gehrig's disease) - which are all incurable presently.

"If we learn how to manipulate PTB, which appears to be a kind of master regulator, we might eventually be able to avoid some of these problems by creating new neurons in patients using their own cells adjacent deteriorating neurons," said Fu.

Funding for this research came, in part, from National Institutes of Health grants and the China 973 programs.

Paper: Yuanchao Xue et al., Direct Conversion of Fibroblasts to Neurons by Reprogramming PTB-Regulated MicroRNA Circuits, Cell, 2013, DOI: 10.1016/j.cell.2012.11.045

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