Researchers identify a missing link in genetic Parkinson’s
The findings may help explain why some dopamine-producing cells are more susceptible to Parkinson’s than others.
A team of researchers at the University of York have shown a protein called Rab10 plays an important role in the loss of brain cells in LRRK2-associated Parkinson’s.
The results, from the Parkinson’s UK-funded study, shine a light on a new avenue of research that, ultimately, could slow or stop Parkinson’s.
A gene linked to Parkinson’s
Parkinson’s is an 'idiopathic' condition, which means that it usually isn’t connected to any particular cause. However, for a small minority, Parkinson’s can be caused by inherited changes in genes. For other people, genetic variations can play a part in increasing the risk of the condition.
A change in the LRRK2 gene known as G2019S is probably the most common genetic variant linked to Parkinson’s. In the UK, around 1 in 100 people with Parkinson’s carry this version of the gene which causes the LRRK2 protein to be more active than normal.
We know that people with this genetic change have an increased risk of developing Parkinson’s. However, how changes in LRRK2 lead to the loss of dopamine-producing brain cells is largely unknown.
Filling in a piece of the puzzle
Dr Chris Elliot and his team have previously observed that a small protein called Rab10 contributes to LRRK2-induced Parkinson’s symptoms in flies. So, in a Parkinson’s UK-funded research project, they set out to investigate how Rab proteins work with LRRK2 and may be involved in the loss of dopamine-producing brain cells.
The team’s latest findings, published in the scientific journal G3: Genes, Genomics, Genetics, show that of all the Rab proteins, Rab10 interacts in the strongest way with the LRRK2 protein. This interaction could be the missing piece of the puzzle that connects LRRK2 with the loss of dopamine-producing brain cells.
Turning understanding into new treatments
There is still much we don’t know about why brain cells are lost in Parkinson’s. For instance, why are some cells lost when other neighbouring cells survive?
Researchers have suggested a number of possible reasons why dopamine-producing brain cells are more affected than others. It could be due to factors such as high dopamine levels, the effects of glutamate or calcium, and even the length and complexity of the brain cells affected. But maybe Rabs have something to do with it.
We know that different types of Rab proteins are found in different dopamine-producing brain cells. And this research suggests, for the first time, that cells containing Rab10 protein may be more vulnerable than cells containing other Rab proteins.
This opens the door to developing potential treatments that might be able to target specific Rab proteins to slow or stop the progression of Parkinson’s, something no current treatment can do.
In many ways, Parkinson’s is like an incomplete jigsaw puzzle. By funding studies that help us understand Parkinson’s, we are adding vital pieces to fill in the gaps, helping us to see the full picture and to develop better treatments that are so urgently needed.