Monday, March 30, 2009

Lighting up Parkinson’s disease research

Most people do not think of jellyfish at the mention of Parkinson’s disease research. But, at the MassGeneral Institute for Neurodegenerative Disease (MIND), researchers Pamela McLean, PhD, and Bradley Hyman, MD, PhD, are using the same fluorescent protein which causes the green glow of jellyfish for their experiments testing potential drugs for the treatment of Parkinson’s disease (PD).

“Looking at the protein alpha-synuclein, we are investigating possible strategies to prevent or stall Parkinson’s disease by using fluorescent proteins,” says McLean. “When alpha-synuclein protein misfolds, it easily sticks to other protein molecules and creates clumps that are toxic to brain cells.”

McLean and her group are using the fluorescent protein by splitting it in half and attaching one half to the end of one alpha-synuclein molecule and the other half to the end of a second alpha-synuclein molecule. When two separate alpha-synuclein proteins misfold and interact, the ends come together resulting in small clumps that glow. Using this technology, McLean has developed experiments to measure these errors and their toxicity to brain cells.

Closely examining the misfolding, McLean has shown one natural way that misfolding damage can be prevented. When the brain activates “chaperone” proteins, these proteins can refold alpha-synuclein correctly or transport it to the cell’s own recycling plant, where damaged cells survive or are appropriately discarded. “Imagine a chaperone at a dance separating two clingy teenagers, and you will have a vivid image of the brain’s chaperone defense,” says McLean. “We are researching whether drugs might activate additional chaperone proteins as a way to protect the brain against the ravages of alpha-synuclein and their resulting diseases.”

McLean is now screening a set of drug compounds that are known to increase chaperone proteins. By treating PD cells with drugs, she hopes to show that increasing chaperones saves brain cells. In these experiments, cells which are not treated with drugs will glow as the alpha-synuclein molecules bind together, meanwhile those treated with effective compounds will remain dark, indicating they are healthy.

For more information about the research being conducted at MIND, access

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