PINK1

Parkinson's disease

Researchers have identified more than 70 mutations in the PINK1 gene that can cause Parkinson's disease, a condition characterized by progressive problems with movement and balance. PINK1 gene mutations are associated with the early-onset form of the disorder, which typically begins before age 50.

Many PINK1 gene mutations alter or eliminate the kinase domain, leading to a loss of protein function. At least one mutation affects the mitochondrial-targeting motif and may disrupt delivery of the protein to mitochondria. With reduced or absent PTEN induced putative kinase 1 activity, mitochondria may malfunction, particularly when cells are stressed. Cells can die if energy is not provided for essential activities. It is unclear how PINK1 gene mutations cause the selective death of nerve cells that characterizes Parkinson's disease. The loss of these cells weakens communication between the brain and muscles, and ultimately the brain becomes unable to control muscle movement.