Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease and Lou Gehrig's disease, is characterised by the progressive loss of motor neurons, which control the body’s voluntary muscles. With this unrelenting cell death comes worsening muscle stiffness, weakening and wasting until the patient can no longer move, speak, swallow or breath normally. It has been discovered that before the neurons die, they develop protein aggregates, or inclusions, which are thought to gum up the cellular machinery, preventing normal function. For example, the protein pictured – hnRNPA2 – is sometimes mutated in ALS, and the mutant version is thought to convert this normally fluid protein, which in cells forms droplet-like structures (shown), into a more sticky, solid disease-associated state. Understanding how the mutation and other modifications to the protein cause this conversion may reveal ways to prevent or reverse it in disease.
Written by Ruth Williams