PARK7

The PARK7 gene provides instructions for making the DJ-1 protein. Studies indicate that this protein has several functions, although none are fully understood. The DJ-1 protein may help protect cells, particularly brain cells, from oxidative stress. Oxidative stress occurs when unstable molecules called free radicals accumulate to levels that damage or kill cells. Additionally, the protein may serve as a chaperone molecule that helps fold newly produced proteins into the proper 3-dimensional shape and helps refold damaged proteins. Chaperone molecules also assist in delivering selected proteins to proteasomes, the cell machinery that breaks down unwanted molecules. Researchers also suggest that the DJ-1 protein may play a role in activities that produce and process RNA, a chemical cousin of DNA.

Parkinson disease - caused by mutations in the PARK7 gene

Researchers have identified more than 10 PARK7 mutations that cause early-onset Parkinson disease. In some cases, a large portion of the PARK7 gene is deleted, and no functional DJ-1 protein is made. Other mutations lead to an abnormally small DJ-1 protein or change the building blocks (amino acids) used to make the protein. The altered protein is unstable and does not function properly, if at all.

It is unclear how loss of functional DJ-1 protein leads to Parkinson disease. Some researchers suggest that PARK7 mutations disrupt the protein's chaperone function, which leads to a toxic buildup of misfolded or damaged proteins and eventually, to cell death. Another possibility is that PARK7 mutations impair the protein's ability to protect cells from destructive oxidative stress. Nerve cells that make the chemical messenger dopamine are particularly vulnerable to oxidative stress. With diminished protection, free radicals may cause enough damage to kill these nerve cells. Loss of dopamine-producing nerve cells is a characteristic feature of Parkinson disease.