CRISPR technology identifies crucial genes linked to Parkinson's disease

Researchers in the US have utilized advanced CRISPR interference technology to discover a new collection of genes that enhance the likelihood of developing Parkinson's disease.

Over 10 million individuals globally are affected by Parkinson’s disease. It is the second most prevalent neurodegenerative disorder following Alzheimer’s disease.

For many years, researchers have been exploring why certain individuals with pathogenic variants develop Parkinson’s disease, whereas others with the same variants do not. The dominant theory indicates that other genetic factors might have an influence.

The research, published in the journal Science, uncovers a new group of genes and cellular pathways that contribute to the risk of developing Parkinson’s disease.

Researchers at Northwestern University examined the complete human genome employing CRISPR interference technology.

They found that a cluster of 16 proteins, named Commander, collaborates to serve a previously unknown function in transporting certain proteins to the lysosome -- a cellular component that functions as a recycling hub -- dismantling waste materials, aged cell components, and other undesired substances.

"Our research shows that various genetic elements contribute to the development of conditions such as Parkinson’s disease, indicating that treatment strategies should focus on multiple critical pathways for these ailments," stated Dr. Dimitri Krainc, chair of the Davee department of neurology and director of the Feinberg Neuroscience Institute at the university.

Instead of studying tens of thousands of patients, which could be challenging and costly, the team resorted to CRISPR. “We used a genome-wide CRISPR interference screen to silence each of the protein-coding human genes in cells and identified those important for PD pathogenesis,” Krainc said.

By examining the genomes from two independent cohorts the scientists found loss-of-function variants in Commander genes in people with Parkinson’s compared to those without it. “This suggests that loss-of-function variants in these genes increase Parkinson’s disease risk,” Krainc said.