Stem Cells to Nerve Cells

Small synthetic molecule initiates differentiation of adult neuronal rat brain cells to neurons

28-Dec-2005

Adult neuronal stem cells have the potential to mature into functional nerve cells (neurons) and neuron support cells (astroglia). The mechanisms for this process are thus far not well understood. Researchers at the Scripps Research Institute in the USA have now synthesized an agent called neuropathiazol, a small molecule that induces neuronal rat brain stem cells to selectively differentiate to form neurons.

To date, no cure has been found for neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, or multiple sclerosis. Researchers have a bit of hope for stem cell therapy. Stem cells have the ability to divide throughout a lifetime without being differentiated, meaning that they can in principle develop into any desired type of cell. Neuronal stem cells from certain regions of the adult brain are in a position to differentiate into neurons, astrocytes (cells that support neurons), or glial cells (which form the electrical insulation around neuronal processes). Some substances, including retinoic acid, are known to initiate or guide differentiation, but none of these offers sufficiently high activity or selectivity.

Peter G. Schultz and his team were looking specifically for a molecule that allows neuronal stem cells to mature exclusively into neurons. To this end, they used high-throughput screening to comb through a substance library containing 50,000 heterocyclic compounds. Droplets of the dissolved substances were added to tiny cell cultures of neuronal rat brain stem cells. A special change to the cells' morphology and a reaction to specific immunostains made it possible to detect cultures with differentiated neurons. A class of 4-aminothiazolenes seemed promising. Starting from the "hits" in the screening, the researchers synthesized additional similar compounds, which they again screened. In the end they identified a particularly active compound; under the influence of neuropathiazol, more than 90% of the neuronal stem cells matured into neurons. Unlike retinoic acid, neuropathiazol does not lead to formation of astrocytes or glial cells; it even inhibits maturation to astroglia if their differentiation has already been initiated by another agent. The researchers now hope to use neuropathiazol to better understand the mechanisms involved in the differentiation of neuronal stem cells to neurons - with the goal of developing stem cell therapies for the treatment of neurodegenerative diseases.

Original publication. P. G. Schultz; "A Synthetic Small Molecule That Induces Neuronal Differentiation of Adult Hippocampal Neural Progenitor Cells"; Angewandte Chemie International Edition 2005.

https://www.bionity.com/en/news/51090/stem-cells-to-nerve-cells.html