PARK7

Parkinson's disease

Researchers have identified more than 25 PARK7 gene variants (also called mutations) that can cause Parkinson's disease, a condition characterized by progressive problems with movement and balance. These variants are associated with the early-onset form of the disorder, which begins before age 50. Some PARK7 gene variants 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. Other variants delete a large portion of the PARK7 gene, preventing the production of any functional DJ-1 protein.

It is unclear how loss of functional DJ-1 protein leads to Parkinson's disease. Some studies suggest that PARK7 gene variants 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 gene variants 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. Progressive loss of dopamine-producing nerve cells is a characteristic feature of Parkinson's disease. The death of these cells weakens communication between the brain and muscles, and ultimately the brain becomes unable to control muscle movement.