Metallic probe compound helps spectroscopic study of Parkinson’s disease

Houston, TX--Researchers at Rice University have developed a spectroscopic technique that lets them look inside living cells and see the insoluble fibrillar deposits associated with Parkinson's disease.¹

The researchers designed a molecular probe based on the metallic element ruthenium. Testing inside live neuroglioma cells, they found that the probe binds with the misfolded alpha-synuclein proteins that clump together and form fibrils and disrupt the cell’s functions. The ruthenium complex lit up when triggered by a laser -- but only when attached to the fibril, which allows aggregation to be tracked using photoluminescence spectroscopy.

The achievement built on the development by Rice researcher Angel Marti and colleagues of metallic compounds that switch on to emit light when they attach to misfolded proteins -- for example, the beta amyloids that form plaques in the brains of Alzheimer’s sufferers.

“The connection between Parkinson’s and Alzheimer's is natural, although they are very different diseases because Alzheimer’s beta amyloid peptides are extracellular, while the onset of Parkinson’s is associated with alpha-synuclein protein inside cells,” says Angel Martí, one of the researchers. “We always thought we could apply the same techniques we used for beta amyloids to probe the aggregation of other proteins."

“There are a few compounds you can use to detect the presence of these types of protein aggregates, but none of them have been reported to work in cells,” adds Laura Segatori, another researcher. “When you’re thinking about developing a therapeutic strategy, you want to be able to detect the presence of fibril aggregates in living cells, or even in animals. It’s been very nice to collaborate with someone with the expertise to do this.”

Segatori has made important strides in the study of diseases caused by proteins that misfold and clump together. Alzheimer’s, Parkinson’s and Gaucher diseases are examples, all the result of genetic mutations or conditions that disrupt the way proteins fold and keep them from performing their functions.

The Rice group sees the possibility that metallic complexes can be tailored to tag aggregates implicated in other degenerative diseases. “Metal complexes are like Legos, in the sense that you can attach whatever you want to them,” says Nathan Cook, lead author of the paper.

REFERENCE:

1. Nathan P. Cook et al., Journal of the American Chemical Society (2012); DOI: 10.1021/ja3100287