Abandoning the Proteinopathy Paradigm in Parkinson Disease —Not So fast

To the Editor Espay and Okun recently proposed abandoning the proteinopathy paradigm in Parkinson disease (PD) in favor of a “proteinopenia” hypothesis. Loss of function as a possible mechanism for PD and other neurodegenerative diseases is not a new idea, and we agree that multiple potential mechanisms underlying neurodegeneration should be investigated. Although their theory is provocative, they vastly oversimplify complex topics and selectively cite/interpret studies with serious limitations to reach an ill-supported conclusion that would stifle our best developed line of therapeutic investigation. From the first sentence, the authors flatten all the complexity of the protein-folding field. In fact, many prot eins only function once assembled into higher-order structures, and numerous studies have uncovered physiological functions that emerge when proteins form amyloidogenic structures. A complex field cannot be oversimplified into such black-and-white opposition as “proteinopathy” vs “proteinopeni a.”
Source: JAMA Neurology - Category: Neurology Source Type: research