Link between RAB32 mutation, Parkinson’s focus of research grant
Canadian researcher will study how immune cells in brain are affected
A three-year grant from Parkinson Canada will allow a Canadian researcher to investigate the mechanisms by which a recently found mutation in the RAB32 gene is linked to Parkinson’s disease.
The $135,000 grant will allow Jay Penney, PhD, associate professor at the University of Prince Edward Island in Canada, to understand how the RAB32 mutation affects the function of neurons and microglia, the resident immune cells in the brain, and increases the risk for Parkinson’s.
“The idea is to see how the mutation affects these cells, and by understanding that, we can begin to piece together how it contributes to disease,” Penney said in a university news story. “This research could help us better understand how Parkinson’s develops at a cellular level, and then potentially treat it.”
RAB32 gene mutation linked to increased Parkinson’s risk
Parkinson’s disease is caused by the progressive loss of dopaminergic neurons, the nerve cells responsible for producing dopamine, a signaling molecule involved in motor control. While in most cases, Parkinson’s disease is sporadic, about 15% of the patients carry a genetic mutation that increases their risk of developing the disease.
One of the most common genetic causes are mutations in the LRRK2 gene, which is linked to the activation of the LRRK2 enzyme. More recently, a mutation in the RAB32 gene, called Ser71Arg, which also activates LRRK2, was linked to a 13.2 times increased risk for Parkinson’s. Based on a global study, the RAB32 Ser71Arg mutation was more than 100 times more prevalent in people with Parkinson’s than in the general population.
RAB32 is a protein that helps move materials inside cells and supports the immune system. It is found in high levels in microglia, where it helps fight infections by sending microbe-fighting substances to where harmful microbes are hiding.
This is the first step in understanding how things are happening on a cell level. If we can do that, then maybe down the road we can figure out how to find a cure.
In the now-funded project, Penny will use human stem cell models to create neurons and microglia to understand how RAB32 mutations disrupt the cells’ function and lead to Parkinson’s. Stem cells have the unique ability to develop into different types of specialized cells.
Although mouse models are traditionally used to study the disease, findings from mouse studies often do not directly translate into human disease. “
With stem cell models, we can study human cells directly. That’s crucial for making discoveries that will actually apply to patients,” Penney said.
Although the project is in its initial stages, Penney hopes it may contribute to identifying potential targets for the development of new treatments for Parkinson’s disease.
“This is the first step in understanding how things are happening on a cell level. If we can do that, then maybe down the road we can figure out how to find a cure,” he said.
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