Protein Affected By Rare Parkinson’s Mutation May Lurk Behind Many Cases of the Disease

Mutations in the gene LRRK2 have been linked to about 3 percent of Parkinson’s disease cases. Researchers have now found evidence that the activity of LRRK2 protein might be affected in many more patients with Parkinson’s disease, even when the LRRK2 gene itself is not mutated.

The study was published in Science Translational Medicine and was supported in part by NINDS.

“This is a striking finding that shows how normal LRRK2 may contribute to the development of Parkinson’s disease,” said Dr. Beth-Anne Sieber, NINDS program director. “This study also identifies LRRK2 as an integral protein in the neurobiological pathways affected by the disease.”

More than 10 years ago, researchers linked mutations in the LRRK2 gene with an increased risk for developing Parkinson’s disease. Those mutations produce a version of LRRK2 protein that behaves abnormally and is much more active than it would be normally.

Despite its importance in Parkinson’s disease, the very small amount of normal LRRK2 protein in nerve cells has made it difficult to study.

In the current study, the authors developed a new method for observing LRRK2 cells that makes them glow fluorescently only when LRRK2 is in its activated state. They have also used detection of fluorescent signals to demonstrate loss of binding of an inhibitor protein to LRRK2 when LRRK2 is activated.