A study conducted by scientists at St. Jude Children’s Research Hospital indicates that mutations in the TDP-43, the gene reported to be responsible for amyotrophic lateral sclerosis (ALS), disrupt the RNA transport system in nerve cells. Researchers note that study results suggest that the mutations disrupt efficient movement within nerve cells of RNA molecules.

The hospital reports that researchers worked in motor neurons derived from ALS patients to demonstrate how each of three different TDP-43 mutations impaired delivery of RNA molecules to their final destination near the junction where a nerve and its target muscle meet. The results also indicate how issues in RNA metabolism, including disturbances in RNA regulation and functioning, lead to ALS and other neurodegenerative diseases.

J. Paul Taylor, MD, PhD, corresponding study author, member of the St. Jude Department of Developmental Neurobiology, states, “Five years of tremendous progress in ALS genetics has revealed that RNA metabolism is a critical pathway that is impaired in this disease.”

Taylor adds that in light of the complex process of RNA metabolism, the study offers a more refined understanding of how ALS-causing mutations impair RNA metabolism, “so we know what needs fixing therapeutically.”

The hospital notes that the work for the study was done in motor neurons from the fruit fly Drosophila melanogaster, mouse brain cells, and human neurons produced by reprogramming cells from ALS patients with three different TDP-43 mutations.

The study appears in Neuron

Source: St. Jude Children’s Research Hospital