APDA-funded research conducted by Dr. Talene Yacoubian of the University of Alabama School of Medicine at Birmingham – one of APDA’s Centers for Advanced Research – suggests a new approach to understanding the basic biology of Parkinson’s disease.
Lewy bodies, the pathologic hallmark of Parkinson’s disease (PD), are made up of clumps of a misfolded protein called alpha-synuclein (αsyn). Much current PD research is dedicated to figuring out how and why αsyn misfolds, how the misfolded protein forms aggregates, and what happens in the cell once the aggregations are present. Alpha-synuclein (αsyn) however, is found throughout the normal brain and the vast majority of time, does not contribute to disease. Exploring the mechanisms that keep αsyn folded correctly could be even more crucial to our understanding of how to fix the problems that occur in PD, than figuring out what goes wrong.
Dr. Talene Yacoubian of the University of Alabama School of Medicine at Birmingham, took this approach in her recently published study, partially supported by the American Parkinson Disease Association. It has been long known that there exists a group of proteins in the cell, known as chaperone proteins, whose function is to ensure that other proteins fold correctly. One such family of chaperone proteins, which contains seven members, is called 14-3-3. Dr. Yacoubian investigated whether 14-3-3 proteins, and specifically 14-3-3θ, helps αsyn stay in its correct shape.
Two established cell culture systems previously developed to study αsyn biology were used to probe the role of 14-3-3θ in αsyn processing. In these systems, 14-3-3θ reduced the clumping of αsyn and the αsyn was less toxic to nerve cells. When the reverse experiments were performed and 14-3-3θ was inhibited in the cell models, the released αsyn tended to clump more and was more toxic to nerve cells.
Dr. Yacoubian’s data suggests that the 14-3-3 group of proteins plays a role in keeping αsyn in its proper shape. More studies are necessary, but next steps may involve attempts to increase the levels of 14-3-3 in the cell to help to keep αsyn in check. APDA is proud to support the work of Dr. Yacoubian and the PD researchers at University of Alabama School of Medicine at Birmingham, one of APDA’s eight Centers of Advanced Research.