Revealing the role of protein clearance pathways in sporadic ALS

The major defining pathological hallmark of ALS is the presence of abnormal accumulation of proteins within motor neurons. These proteins are tagged with a molecule called ubiquitin. Cells label proteins with ubiquitin to mark that protein for degradation, as part of the normal “recycling” process within cells. This suggests that disruption in protein recycling may be an underlying cause of ALS.
Confirming this, we have recently identified genetic mutations in one of the cell’s protein recycling pathways that cause inherited ALS. This project will examine protein profiles to identify whether this same pathway is altered in sporadic ALS patients.