U of A research discovers another role of brain molecule in neurodegeneration

A research team from the University of Alberta has discovered another function of ganglioside molecules in brain regulation and neurodegenerative diseases prevention. 

According to Simonetta Sipione, a professor in the department of pharmacology and a member of the Neuroscience and Mental Health Institute and the Glycomics Institute of Alberta, they discovered in their previous study that gangliosides are less abundant in the brain of people with Huntington’s disease, a genetic disorder that affects physical movement and cognition.

Gangliosides are vital molecules found in the brain and in the nervous system. They are embedded in the plasma membrane and are crucial in cell signalling, cell-to-cell communication, and cell membrane regulation. 

Another neurodegenerative condition where the gangliosides are affected is Parkinson’s disease, which impairs motor co-ordination. 

“We wanted to better understand the functions of this molecule to understand what goes wrong in Huntington’s, in Parkinson’s, or in those diseases where the gangliosides are decreased or missing,” Sipione said.

They had worked earlier with mouse models that had Huntington’s disease and determined that the subjects had lower levels of GM1, a type of ganglioside, in comparison to normal brains. They also found that when more of these molecules were injected into the brain of the mice, the normal levels of gangliosides were restored and their symptoms of Huntington’s disease improved.

However, their findings were limited and they weren’t able to determine how the levels of gangliosides directly affect the development of neurodegeneration.

U of A research team working to discover potential treatments for neurodegenerative diseases

In this most recent study that started four years ago, they found that gangliosides regulate the extracellular vesicle secretion of cells which are used in cell-to-cell communication. Such vesicles are also used in waste transportation as they contain cellular waste, including misshapen proteins that bring about neurodegeneration.

According to Sipione, these findings can be the foundation of the development of treatment for diseases caused by misshapen proteins. The idea for anti-neurodegenerative therapies was to administer exogenous ganglioside molecules to cells in order to reestablish the normal amounts of gangliosides, which will then restore cell-to-cell communication and extracellular vesicle formation.

Their research team is also working on a different study to explore the other functions of gangliosides in various contexts, such as their roles in limiting brain inflammation. 

She said that these discoveries draw inspiration for them to continue in this line of research. 

“We think that this is an important line of investigation, with potential therapeutic developments,” Sipione said.

“Understanding how these molecules work to keep our brain healthy [is] important to potentially develop strategies in the future to maintain healthy levels of gangliosides in the brain, so preventing their reduction in neurodegenerative diseases, or using exogenous gangliosides as a therapy to restore normal levels in the brain and promote the gangliosides beneficial actions.”