Helping the Brain fight Parkinson’s — Investigating the effect of USP8 on Parkin Function

Dr Thomas M. Durcan,
Montreal Neurological Institute

At the Montreal Neurological Institute, neuroscientist Thomas Durcan studies the mechanisms within the human brain that can be exploited to protect it from the impact of Parkinson’s disease. This work focuses on a protein called Parkin, which removes damaged components from cells, as well as a partner enzyme that appears to guide this protein’s activities. He suggests that this enzyme could be a worthwhile target for new drugs or other therapies that could enhance Parkin’s ability to protect against the effects of Parkinson’s.

An ideal treatment for Parkinson’s disease would be identifying a protein that could be exploited to promote the survival of the brain cells that die as Parkinson’s progresses. Durcan is sorting through the biochemical details of how that might be possible.

His work focuses on Parkin, a protein that plays a key role in removing the cellular damage Parkinson’s causes. Such damage can disrupt the normal function of mitochondria, a vital structure within cells that manage energy use and the transmission of signals to other cells. Parkin manages the removal of damaged mitochondria and associated cargo within cells. Without this protection, the cells can die.

Durcan’s research builds on studies of Parkin’s behaviour. Other research has uncovered the fact that deubiquitinating enzymes, also known as DUBs, can regulate the protective effects of Parkin in a number of pathways, including its ability to remove damaged mitochondria.

“What we wondered was, if Parkin had a specific partner to regulate its activity, then maybe by targeting that partner we could use Parkin for therapies,” Durcan explains.

For Durcan, whose background is in cell biology, this work represents an exciting frontier. He had previously worked on cancer, but the more intriguing, unanswered questions accompanying Parkinson’s disease attracted him to this different field. He contrasts the investigation of these two fields by pointing out that cancer features cell growth, which means there is plenty of material to analyze, while Parkinson’s is characterized by the loss of affected brain cells. The loss of these cells makes it nearly impossible for researchers to access human brain cells affected directly by Parkinson’s that they can study.

The use of stem cells to replicate large numbers of these affected brains cells for laboratory purposes is overcoming the problem of small amounts of tissue to study in Parkinson’s.

“They’re not perfect neurons, by any means,” says Durcan. “But at the moment they’re the closest thing we have to a bona fide human model.”

As part of his job, Durcan works with people with Parkinson’s to explain this new science of stem cells to them, an exchange that he finds highly satisfying.

“I wanted to get into a field where there was still a lot to uncover,” he says, noting that the last decade has been one of solid progress toward understanding Parkin and its role in cell biology. “You feel like you’re inching closer to some kind of treatment or a way we can modify the disease.”

Read about other researchers recently funded by the Parkinson Canada Research Program by visiting the research section of