The Genetic Link to Parkinson’s Disease | Johns Hopkins Medicine

If you have family members with Parkinsons disease, or if you yourself have the disease and are concerned about your childrens chances of developing it, youve probably already wondered: Is there a gene that causes Parkinsons disease? How direct is the link?

About 15 percent of people with Parkinsons disease have a family history of the condition, and family-linked cases can result from genetic mutations in a group of genes LRRK2, PARK2, PARK7, PINK1 or the SNCA gene (see below). However, the interaction between genetic changes, or mutations, and an individuals risk of developing the disease is not fully understood, says Ted Dawson, M.D., Ph.D., director of the Institute for Cell Engineering at Johns Hopkins.

Heres what you need to know:

Theres a long list of genes known to contribute to Parkinsons, and there may be many more yet to be discovered. Here are some of the main players:

SNCA: SNCA makes the protein alpha-synuclein. In brain cells of individuals with Parkinsons disease, this protein gathers in clumps called Lewy bodies. Mutations in the SNCA gene occur in early-onset Parkinsons disease.

PARK2: The PARK2 gene makes the protein parkin, which normally helps cells break down and recycle proteins.

PARK7: Mutations in this gene cause a rare form of early-onset Parkinsons disease. The PARK7 gene makes the protein DJ-1, which protects against mitochondrial stress.

PINK1: The protein made by PINK1 is a protein kinase that protects mitochondria (structures inside cells) from stress. PINK1 mutations occur in early-onset Parkinsons disease.

LRRK2: The protein made by LRRK2 is also a protein kinase. Mutations in the LRRK2 gene have been linked to late-onset Parkinsons disease.

Among inherited cases of Parkinsons, the inheritance patterns differ depending on the genes involved. If the LRRK2 or SNCA genes are involved, Parkinsons is likely inherited from just one parent. Thats called an autosomal dominant pattern, which is when you only need one copy of a gene to be altered for the disorder to happen.

If the PARK2, PARK7 or PINK1 gene is involved, its typically in an autosomal recessive pattern, which is when you need two copies of the gene altered for the disorder to happen. That means that two copies of the gene in each cell have been altered. Both parents passed on the altered gene but may not have had any signs of Parkinsons disease themselves.

Our major effort now is understanding how mutations in these genes cause Parkinsons disease, says Dawson. SNCA, the gene responsible for making the protein that clumps in the brain and triggers symptoms, is particularly interesting.

Our research is trying to understand how alpha-synuclein works, how it travels through the brain, says Dawson. The latest theory is that it transfers from cell to cell, and our work supports that idea. Weve identified a protein that lets clumps of alpha-synuclein into cells, and we hope a therapy can be developed that interferes with that process.

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The Genetic Link to Parkinson's Disease | Johns Hopkins Medicine