Why is it so difficult to discover drugs for amyotrophic lateral sclerosis? A protein intrinsic disorder perspective

There is a common oversight in current drug discovery methodologies, which is the neglect of intrinsically disordered proteins (IDPs) playing several crucial roles in the pathology of neurodegeneration in general and ALS in particular. Therefore, it seems that the 'one-size-fits-all' approach to ALS is hitting a wall because these 'shapeshifters' of the cellular world are ignored. Consequently, to be more successful in finding drugs treating ALS, gears should be shifted from rational structure-based models to intrinsic disorder-centric approaches.