Changes in a gene linked to young onset Parkinson’s

The causes of Parkinson’s are not yet fully understood. However, previous research has identified a number of different genes that are linked to the condition. Changes to these genes may cause or increase risk of Parkinson’s. Read more about genetics and Parkinson’s.

Results from a study we funded show that a gene, called PSMF1, is linked to young onset Parkinson's. This is the first time the PSMF1 gene has been linked to Parkinson's, potentially opening up new targets for future treatments.

What is the PSMF1 gene?

The PSMF1 gene provides the information to create a small protein, a building block of all cells. The protein plays an important role in regulating a system called the proteasome, which normally stops cells becoming clogged with excess waste. Making sure the proteasome works properly is particularly important in brain conditions like Parkinson’s, where troublesome proteins build up inside brain cells and cause damage.

What did researchers find?

Researchers investigated what happens when there are changes to the PSMF1 gene. They found that these changes had 2 outcomes:

• Problems with proteasomes - not only were there not as many, but the proteasomes that were present also didn’t function normally. Meaning the cells were less able to clear away unwanted proteins.
• Malfunctioning mitochondria - mitochondria, responsible for producing the energy that cells need to work, didn’t function as well as they should. Mitochondria are particularly important in brain cells affected by Parkinson’s, which require high levels of energy to function.

The researchers found that, when the PSMF1 gene was removed in flies and mice, the animals showed movement problems, and a loss of brain cells. They also found that those with changes in both copies of their PSMF1 genes developed Parkinson’s earlier, suggesting a possible link with young onset Parkinson’s.

Read the full scientific paper in Nature Communications.

An additional study demonstrated that increasing PSMF1 levels by delivering a working copy of the gene improved movement problems and survival rate in a mouse model of Parkinson’s. This highlights the potential of the PSMF1 gene to be a target for new treatments beyond PSMF1-related Parkinson’s. 

What does this mean for people with Parkinson’s?

The findings suggest that changes to the PSMF1 gene may play a role in the development of neurological conditions, including young onset Parkinson’s. This opens up a new avenue of research, targeting treatments that counteract the problems caused by the PSMF1 gene or improve how the proteasome functions.

Emma Rodgers, Research Communications Manager at Parkinson’s UK, comments:

"It’s really positive to see research that we’ve funded contribute towards our understanding of the genetics of Parkinson’s, especially young onset Parkinson’s. 

"By demonstrating that changes to the PSMF1 gene lead to problems in cells that can cause damage, we can start to explore how these gene changes may increase the risk of Parkinson’s, and explore potential new treatments that target this gene and the proteasome."

Dr Francesca Magrinelli, Professor Kailash Bhatia and Professor Henry Houlden, lead researchers at University College London, said:

"Our study suggests that changes in the PSMF1 gene may affect how brain cells stay healthy and highlights that proteasome regulation is key not only in this specific form of young onset Parkinson’s but also in the more common, non-genetic forms. While more research is needed, this gives us a clearer direction for exploring new mechanisms of Parkinson's and targeted treatments in the future.

"We're grateful to Parkinson’s UK for supporting this research and helping us take an important step forward in understanding young onset Parkinson’s. We hope this work brings us closer to better support and, ultimately, improved outcomes for people living with Parkinson’s and their families."