In 1997, researchers at the National Institutes of Health made the first Parkinson’s genetic connection, discovering that mutations in the SNCA gene were common in several families who had many members with Parkinson’s. While mutations in this gene are rare, they have taught us invaluable information about PD.
The SNCA gene instructs the body to make the protein alpha-synuclein, which for reasons that are not yet known, clumps in the brain cells of people with PD. Study of the SNCA gene led to this understanding that applies to nearly all people with the disease. Since then, alpha-synuclein has been a major target of new drugs for Parkinson’s.
LRRK2 (LRRK2 protein)
Another gene that plays a role in Parkinson’s is LRRK2, which accounts for one to two percent of all cases. For people of particular ethnic backgrounds — Ashkenazi (Eastern European) Jewish and North African Berber descent — mutations in the LRRK2 gene account for a much greater number of cases than in the general PD population. Mutations in LRRK2 lead to too much activity of the LRRK2 protein, though recent research indicates people without a mutation can also have overactivity of LRRK2.
Shake It Up are funding several studies into LRRK2 and you can learn more about these here.
Mutations in the glucocerebrosidase beta (GBA) gene are the most common of the currently known PD genetic mutations and also more common in people of Ashkenazi Jewish descent. GBA mutations increase a person’s risk of Parkinson’s, but less so than mutations in SNCA or LRRK2. The GBA gene instructs production of the glucocerebrosidase (GCase) protein, and mutations are associated with not enough GCase activity.
A common genetic contributor to young-onset Parkinson’s (diagnosed before age 50) is a mutation in the PRKN gene, which manufactures the parkin protein. Scientists believe the parkin protein plays a role in recycling mitochondria, or the “power plants” of cells. In the same pathway with parkin lies PINK1 — another target where researchers may be able to intervene to boost parkin activity.