October 30, 2012

I’ve posted a lot of images from papers on human disease models lately, and that’s a good thing. Despite what you may hear from politicians mocking research using fruit flies, worms, or tiny fish, the power of model systems to study a human problem is undeniable to anyone with half a clue. All science on the continuum from basic research all the way to clinical trials is valuable…so thank your favorite scientist today! Today’s image is from a zebrafish paper that identifies a new pathway that may be a good therapy target for muscular dystrophies.

Muscular dystrophies are fairly common diseases that result in the weakening of the protein complexes that connect muscles to their underlying environment, called the extracellular matrix (ECM). The degeneration of muscle-ECM attachment eventually leads to progressive loss of muscle movement and locomotion for the patient. A recent paper identifies a new pathway in muscle-ECM attachment using zebrafish as a model. Goody and colleagues found that biosynthesis of the small molecule NAD+ can reverse muscle degeneration in certain types of dystrophies in zebrafish and even improve swimming. This pathway improves the organization of laminin, an important ECM protein, suggesting the function of an additional laminin receptor complex and pathway from those already studied. Goody and colleagues suggest that this new pathway may serve as a focal point for new muscular dystrophy therapies. In the images above, normal ECM basement membrane tissue adhered normally to both normal muscle cells (blue) and cells with muscle degeneration mutations (red), even after the stress of swimming. This experiment shows the importance of a healthy ECM in restoring function for dystrophic muscles. 

Goody, M., Kelly, M., Reynolds, C., Khalil, A., Crawford, B., & Henry, C. (2012). NAD+ Biosynthesis Ameliorates a Zebrafish Model of Muscular Dystrophy PLoS Biology, 10 (10) DOI: 10.1371/journal.pbio.1001409