Structure of Parkinson’s Protein could lead to new Diagnostic, Treatment options

Chemists have identified the complex chemical structure of the protein that stacks together to form fibrils in the brains of Parkinson’s disease patients. Thus researchers can identify specific targets for diagnosis and treatment. In Parkinson’s, the protein alpha-synuclein forms long fibrils that disrupt brain activity. This is similar to the beta-amyloid fibrils that form in Alzheimer’s disease patients. However, while the beta-amyloid structure is known, the alpha-synuclein structure has eluded researchers as a result of its complexity, its insolubility and the difficulty of characterizing one protein within a fibril.

“This is the first structure of the full-length fibril protein, which is now well established to be important for the pathology of Parkinson’s disease,” said Prof. Chad Rienstra. “Knowing that structure will open up many new areas of investigation for diagnosing and treating Parkinson’s disease.”

The Illinois group used magic-angle spinning nuclear magnetic resonance to measure the placement of atoms in 6 different samples of alpha-synuclein. In each set of samples, they looked at different sets of atoms, then used advanced computational power to put them all together. See a video on YouTube at https://www.youtube.com/watch?v=tZjXeAfqGG4.

The group experimentally verified the structure by producing the protein in the lab and checking it with various imaging methods to see if it matched the fibrils found in Parkinson’s patients. They also verified it biologically by testing it in cell cultures and it indeed behaved like the protein found in patients.

Rienstra’s group is working with the Michael J. Fox Foundation to identify possible diagnostic agents that could target certain spots on the alpha-synuclein protein and would “light up” in a brain scan, allowing for earlier and more accurate diagnosis. “We think that the structure that we resolved of alpha-synuclein fibrils will be really significant in the immediate future and has use for diagnosing Parkinson’s in patients before they’re symptomatic,” Rienstra said. “Once people start having symptoms, whether of Alzheimer’s or Parkinson’s, in many ways it’s a little too late to be effective with therapy. But if you catch it early, I think there’s a lot of promise for therapies that are being developed. Those are all relying upon the structures that we’re solving.” https://news.illinois.edu/blog/view/6367/344159