Rice University scientists have discovered a new way to look inside living cells and see the insoluble fibrillar deposits associated with Parkinson's disease.
The combined talents of two Rice laboratories - one that studies the misfolded proteins that cause neurodegenerative diseases and another that specializes in photoluminescent probes - led to the spectroscopic technique that could become a valuable tool for scientists and pharmaceutical companies.
The research by the Rice labs of Angel Mart- and LauraSegatori appeared online this month in the Journal of the American Chemical Society.
The researchers designed a molecular probe based on the metallic element ruthenium. Testing inside live neuroglioma cells, they found 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 allowed aggregation to be tracked using photoluminescence spectroscopy.
Researchers trying to understand molecular mechanisms of protein misfolding have had limited alternatives to monitor protein aggregation in cells, Mart- said. A probe that can monitor the formation of aggregates should be of great value in the search for drugs that break up fibrils or prevent them from ever forming.
Two years ago, Mart-, an assistant professor of chemistry and bioengineering, and Rice graduate student Nathan Cook revealed their metallic compounds that switch on like a light bulb when they attach to misfolded proteins; that study involved the beta amyloids that form plaques in the brains of Alzheimer's sufferers.
At about the same time, Cook approached Segatori, the T.N. Law Assistant Professor of Chemical and Biomolecular Engineering and assistant professor of biochemistry and cell biology, to ask if she would serve on his dissertation committee. They started talking about his work with Mart-, and Segatori quickly saw the potential of a partnership.
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.
"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," Segatori said. "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."