A gene located on chromosome 6 that is mutated in some people who have Parkinson’s disease, particularly early-onset Parkinson’s. Researchers in Japan first isolated and identified the parkin gene and some of its mutations in the late 1990s when studying a rare form of early-onset Parkinson’s called autosomal recessive juvenile parkinsonism (AR-JP). Because people with AR-JP do not have the classic lewy body structures (protein deposits within brain neurons) that characterize idiopathic Parkinson’s disease, whether AR-JP is a true form of Parkinson’s disease or produces similar symptoms but has a different pathological origin is controversial.
For the parkin gene to clearly cause disease, the person must have identical mutations from both mother and father. Because the number of possible mutations is significant, the conditions necessary for the disease to be manifested happen only in siblings from the same nuclear family and then only in approximately one-quarter of the siblings. However, researchers believe parkin gene mutations of any kind, even just a single mutation from one parent, may increase a person’s vulnerability to Parkinson’s, creating an interaction with environmental factors that causes development of the disease. Scientists have since found numerous defects in structures of the parkin gene called exons, primarily in people with early-onset Parkinson’s, throughout the world. As the technology to identify gene mutations is just becoming available, researchers will be able to examine a wider sample of people, both with and without diagnosed Parkinson’s disease, to attempt to determine how widespread these mutations are.
As does the alpha-synuclein gene mutation, another known gene mutation associated with Parkinson’s disease, the parkin gene mutation alters the way in which neurons handle protein. This alteration, scientists believe, allows toxic levels of oxidative stress to accumulate, leading to premature cell death. Incorrectly oxidized proteins become toxic oxidants, or free radicals, which are capable of causing significant cell and tissue damage over time. Some chromosomal defects also appear linked to whether levodopa therapy is effective. Further research in this area could provide new insights into how and why levodopa functions in the brain and perhaps establish more effective treatment algorithms.