A collaboration of 32 researchers in seven countries has found a genetic mutation they say confers a risk for development of Parkinson’s disease earlier than usual.
The study, published in Brain, is important because the risk comes from a single mutation in the PTEN-induced putative kinase 1 (PINK1) gene. Investigators had believed that this rare form of Parkinson’s developed only when a person inherited mutations in both PINK1 alleles (one from each parent).
PINK1 works with another gene, PARKIN, to ensure that mitochondria in neurons remain healthy. When functioning, proteins from both genes work together to ensure the safe disposal of damaged mitochondria from the cell. Mutations in both PINK1 alleles (or copies) or in both PARKIN alleles mean that the PINK1-PARKIN pathway cannot function, and damaged mitochondria accumulate in a neuron, leading to its death.
This study showed that a specific mutation (p.G411S) in one copy of PINK1 substantially impairs this same pathway by inhibiting the protein produced from other healthy PINK1 allele.
Paper: “Heterozygous PINK1 p.G411S increases risk of Parkinson’s disease via a dominant-negative mechanism”
Reprinted from materials provided by the Mayo Clinic.