Unpacking Brain Damage in ALS

In a recent study published in the journal Neuron, researchers found a common gene mutation in amyotrophic lateral sclerosis (ALS) that generates a deadly protein which may cause the damage in the brain that leads to the disease. In 2011, researchers discovered that about five percent of ALS patients carry an altered version of a gene called C9orf72, which in ALS patients contains hundreds of repeat sequences that are otherwise not present in healthy individuals. However, the original theory, that the C9orf72 mutation in ALS disrupts the gene’s normal function in the cell did not hold up — suggesting that the C9orf72 gene is not essential to neuronal health. The most compelling discovery from the more recent study came from five distinct proteins generated from RNA sequences of the C9orf72 gene. The researchers found that one of the five caused the greatest amount of damage to the cells. The protein chain made from the amino acids proline and arginine, known as a poly-PR chain, accumulated in the nucleolus and rapidly killed the neuron that produced it. By tracking the life cycle of a living neuron in real-time, the researchers could see that as more PR proteins accumulated in the nucleolus, the cell became more bloated and then suddenly died, occurring within 72 hours. To read more about this study, click here.