Canadian Grant to Test Fatty Molecules in Preventing Protein Toxicity in Brain

A University of Alberta pharmacology professor and researcher will use a CA $1.04 million grant to investigate the potential role of fatty molecules — called gangliosides — in treating neurodegenerative diseases, including Parkinson’s disease.

The grant, from the Canadian Institutes of Health Research (CIHR) and worth about $826,000, was given to Simonetta Sipione, PhD, whose training was in biochemistry. Sipione and her team will investigate whether restoring the levels of a particular type of ganglioside, called GM1, can boost the brain’s ability to dispose of toxic proteins, or otherwise prevent them from accumulating to eventually kill nerve cells.

Gangliosides, fat molecules with a sugar link, are highly abundant in the nervous system. They play an important role in the communication between brain cells. However, during aging and in neurodegenerative diseases like Parkinson’s and Huntington’s, the levels of certain gangliosides start to decay.

“Gangliosides are highly enriched in the healthy brain. They help brain cells communicate with each other and with the environment,” Sipione said in a press release.

Boosting the levels of these fatty molecules is a potential strategy to lessen or even halt the onset of these neurodegenerative diseases.

“We are interested in finding out why” these levels drop, and in “developing a viable treatment that tackles the root of the disease, not just the symptoms,” Sipione added.

Sipione’s research is part of GlycoNet, a pan-Canadian research initiative bringing together academics and industry to investigate the potential of glycans — molecules with a sugar component — to treat various diseases.

Her work follows positive results in a mouse model of Huntington’s, in which injection of GM1 into the brain slowed disease progression.

“Restoring the level of GM1 in the brain could be a potential treatment for those who experience, or show signs of, neurodegeneration,” Sipione said.

Researchers believe that gangliosides like GM1 may instruct brain cells to dispose of toxic protein accumulates.

“Toxic proteins are like garbage and your brain is like a house. If garbage accumulates in the house and no one throws it out, your house is going to smell.

“We think GM1 and other gangliosides have a key role in instructing brain cells so that the garbage (toxic proteins) can be thrown out properly and eliminated by trash collectors, which are other biomolecules in the brain,” Sipione said.

“Our studies will help determine the underlying mechanism of GM1’s therapeutic effects and whether other similar molecules could be a novel treatment” for diseases that include Huntington’s, Parkinson’s and Alzheimer’s, she added.