In neurodegenerative diseases like Alzheimers and Parkinson’s, accumulation of aberrant proteins leads to the death of neurons. This same disease process can also be observed in muscles, leading to the break down of muscle cells. One such class of degenerative diseases that affect the muscles are called  myofibrillar myopathies (MFMs).

A new study by researchers at Washington University in St. Louis and University College London has looked at aggregates of proteins in muscle cells to understand how a protein called desmin is involved in muscle degeneration. Based on a host of genetic and structural clues, they suspected that desmin could assemble in muscles in a similar way to how other protein aggregates form in the brain. They ultimately found that desmin aggregates can destroy muscle cells. 

To do this, they first used an algorithm to help them predict forms of desmin they could use to study protein aggregation. Next, in order to look for and measure these aggregations, they used various types of spectroscopy and microscopy. They observed not only desmin aggregates but also the presence of prominent fibrils, or long, thin protein fibers. They were also interested in exactly how desmin aggregated: for example, did a few proteins clump together and then recruit others to join them, or does the aggregate form all at once? Finally, they tested whether the desmin fibrils that they had observed were toxic to skeletal muscle cells. When the desmin aggregates were added, they saw that the muscle fibers collapsed.

This research may help us understand how to more effectively treat MFMs. From a therapeutic standpoint, having a clear picture how these aggregates come together can lead to development of inhibitor drugs. Although MFMs are rare, they can be extraordinarily painful and be life threatening, so advances in treatment of these diseases would substantially help many people.