My Christmas viewing has included (amongst the Strictly, Agatha Christie adaptation, etc) a webinar entitled Fluid Business: Could “Liquid”Protein Herald Neurodegeneration? The webinar is on droplet-like structures inside nerve cells that may be associated with some diseases that kill these nerve cells, such as Alzheimer’s, amyotrophic lateral sclerosis (ALS), etc. The webinar includes short talks by a number of scientists, including a presentation by Peter St George-Hyslop that is based on a very recent paper in Neuron. The report reports a lot of work by a small army of scientists on a protein called FUS. Some mutant variants of FUS are associated with the disease ALS.
The basic idea put forward by the scientists in the webinar is that there is this set of proteins, of which FUS is one, that form liquid droplets inside nerve cells, and these droplets are actually very useful. The droplets may be essential to keep our nerve cells going, and so our brains functioning. So, these liquid droplets are good.
But if the experimentalists are nasty to droplets of the normal FUS protein, the one making droplets in my brain even as I type this, or if they just leave liquid droplets of some mutant FUS’s for a little while, these liquid droplets gel, i.e., they go from liquid to solid like a hot liquid jelly being cooled to room temperature. St George-Hyslop and his army of coworkers present evidence that this gelled protein is bad. It can trap some molecules needed for protein synthesis in the nerve cell.
So, liquid droplets of FUS and similar proteins are good, as they allow the dynamics needed to keep our nerve cells going, but the gelled droplets arrest these dynamics, and the nerve cell could become sick and die. This may be due to the person inheriting a mutant gene for FUS, or due to a very slow process of the liquid gelling that occurs even in our normal FUS droplets. Alzheimer’s, ALS etc, typically strike in old age, when our nerve cells are getting on a bit an, and so less able to fight this tendency for FUS droplets to gel.
It is an interesting and attractive idea. It looks like some sort of nucleation process kicks of in liquid droplets of FUS that gels them, and that if we could understand it better, we could potentially develop drugs to target it and treat these nasty and currently more-or-less untreatable diseases.