Parkinson’s and genetics

Approximately 10-15% of Parkinson’s cases are associated with genetic variations that result in a higher risk of developing the condition. In people with early-onset Parkinson’s (diagnosed before the age of 50), genetic variations are more common than in later onset Parkinson’s.

Genetic material is housed within our DNA, with a gene being a small section of DNA. Genes provide cells with the instructions for making proteins and help ensure the cell functions correctly. However, at times, mutations can arise in genes, resulting in changes to the proteins that are made. It is important to note that having a genetic variation does not immediately mean that someone is going to develop Parkinson’s. There are people who have these variations in their DNA and never show any signs of the condition; researchers are trying to establish the factors that influence this situation.

What are some of the genetic risk factors connected to Parkinson’s?

GBA

Variations to the GBA gene are the most common genetic risk factor for Parkinson’s. The GBA gene provides instructions for making an enzyme called glucocerebrosidase, or GCase. GCase enables cells to clear waste compounds effectively and so if there is a fault in the GBA gene, it results in a faulty waste clearance system in cells. Researchers have been looking to identify medicines that can enhance the level of GCase activity in the body thereby potentially slowing the progression of Parkinson’s. One example of this is the cough medication Ambroxol, which Cure Parkinson’s is currently supporting.

LRRK2

Genetic variations within the LRRK2 gene account for approximately 4% of all Parkinson’s cases with a known genetic cause. People with mutations in the LRRK2 gene are at increased risk of Parkinson’s, however not everybody will go on to develop the condition.

PINK1

The PINK1 gene provides instructions for cells to make a protein called PTEN induced putative kinase 1(PINK1). PINK1 is found in cells throughout the body but when needed, it can move to the mitochondria. The mitochondria are the ‘battery packs’ of all cells, producing the energy they need to function. Scientists believe PINK1 protects mitochondria when cells are under stress, aiding in the removal of any damaged mitochondria. Therefore, mutations in the PINK1 gene could mean that there is a build of damaged mitochondria in a cell. Mutations of the PINK1 gene run in families, however they are rare. Scientists believe they may contribute to early-onset Parkinson’s.

PRKN

The PRKN gene is responsible for making a protein called parkin and many PRKN gene variants have been linked to Parkinson’s. Mutations in PRKN are the most common genetic variations associated with early-onset Parkinson’s and people who have this gene may experience early symptoms such as slowness of movement and freezing. Research has shown that PRKN gene variants cause a dysfunctional version of the parkin protein which may affect the production of dopamine. In people with

Parkinson’s, the brain gradually stops making dopamine leading to the characteristic problems of Parkinson’s, associated with movement and balance. PRKN also commonly works with PINK1 and so variants in the PRKN gene may also be linked to a build-up of damaged mitochondria. Researchers are studying treatments that could enhance parkin protein activity.

SNCA

The discovery of variations in the SNCA gene within families of people with Parkinson’s was the first genetic link to be made for Parkinson’s. The SNCA gene is responsible for providing cells with the instructions for making the protein alpha-synuclein. Issues with alpha-synuclein are a hallmark characteristic of Parkinson’s, with misfolded or dysfunctional copies of the protein accumulating within neurons, forming Lewy bodies. These bodies interfere with cell processes, eventually leading to cell death if not cleared.

Researchers have identified two main types of SNCA variations associated with a higher risk of developing Parkinson’s: those which cause alpha-synuclein to misfold and those that cause it to be overproduced. Some SNCA mutations are also closely associated with young onset Parkinson’s.

How can learning more about these gene variations help treat Parkinson’s?

Understanding what the connections are between Parkinson’s and the underlying genetics can help us to better understand how the condition develops and progresses, and how we can treat, and ultimately cure, it. There are now a number of clinical trials testing drugs in people with Parkinson’s who also have certain gene mutations.