PTEN induced putative kinase 1 (PINK1), also known as PARK6, is causally linked to familial Parkinsonism, and heterozygous loss of PINK1 is a risk factor for sporadic Parkinson's disease.
However, the identification of recessive pathogenic mutations in the pink1 gene in familial PD cases firmly re-ignited interest in the pathophysiology of mitochondria in PD.
We have now tested a candidate interactor protein of PINK1, the mitochondrial translation initiation factor 3 (MTIF3) for involvement in PD pathogenesis.
Although it remains difficult to conclusively demonstrate the pathogenicity of heterozygous mutations, the results of this study and the previously reported subclinical nigrostriatal dysfunction in carriers of heterozygous PINK1 mutations suggest the possibility that these heterozygous mutations are a significant risk factor in the development of later onset PD.
We analyzed whether six different genetic variants within and surrounding PINK1 contribute to the risk of sporadic PD in a Finnish case-control series.
In addition, we show that PINK1 is detected in a proportion of Lewy bodies in cases of sporadic Parkinson's disease and Parkinson's disease associated with heterozygous mutations in the PINK1 gene, which are clinically and pathologically indistinguishable from the sporadic cases.