Mutation analysis and association studies of nuclear factor-kappaB1 in sporadic Parkinson's disease patients.

Biochemical and morphological studies revealed that oxidative stress and apoptosis play a role in neurodegeneration in Parkinson's disease (PD). Reactive oxygen species may be directly involved in apoptosis or via upregulation of toxic cytokines, i.e. tumor necrosis factor alpha (TNFalpha). We recently demonstrated that the TNFalpha pathway contributes to the pathogenesis of sporadic PD using a genetic approach. These signalling pathways converge to the transcription factor nuclear factor kappaB (NF-kappaB), which has been found activated in affected neurons in PD. We performed a detailed mutation analysis of the p50 subunit of NF-kappaB (NFKB1 gene) in 96 sporadic PD patients. Previously, positive association was demonstrated in this cohort to chromosome 4q21-23 containing the NFKB1 gene. We identified three base exchanges not affecting the amino acid sequence, which were found at similar frequencies in controls. Our study does not support a genetically definable role of NFKB1 in the pathogenesis of sporadic PD.