MDA awarded $358,653 to Wilfried Rossoll, assistant professor at Emory University in Atlanta, for research into the effects on nerve cells, or "motor neurons," of toxic TDP43 protein, implicated in ALS (amyotrophic lateral sclerosis, or Lou Gehrig's disease).
"Recently, we have developed novel tools to study protein localization, trafficking and function in cultured primary motor neurons," Rossoll said. "Funding from MDA will now allow us to apply these methods to address the biological role of the ALS disease protein TDP43 in motor neurons."
TDP43 protein is present in all body tissues and serves multiple roles in the processing of messenger RNAs (mRNAs), the molecules that carry genetic information from DNA to the sites of protein synthesis. However, the function of TDP43 in motor neurons and vulnerability of those cells to the protein still is not understood.
"Most studies on the role of TDP43 protein have used non-neuronal cell lines, so its function in the highly specialized motor neuron cell type remains unclear," Rossoll said. "We will use cell cultures of primary motor neurons and motor neurons generated from stem cells to study the function of TDP43 in this cell type, and to gain information about its involvement in ALS."
Preliminary data generated by Rossoll's team suggests that TDP43 plays a role in mRNA processing in the long axon fibers that conduct electrical impulses to muscle cells. The team will test the hypothesis that decreased levels of TDP43 in mRNA-protein complexes in these axons may contribute to the degeneration of motor neurons in ALS.
Increased understanding of the molecular and cellular functions of TDP43 could help lead to the development of therapies that delay or even prevent motor neuron degeneration in people with ALS or other neurodegenerative diseases.
Funding for this MDA grant began August 1, 2010.