Mutation analysis and association studies of nuclear factor-κB1 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 α (TNFα). We recently demonstrated that the TNFα pathway contributes to the pathogenesis of sporadic PD using a genetic approach. These signalling pathways converge to the transcription factor nuclear factor κB (NF-κB), which has been found activated in affected neurons in PD. We performed a detailed mutation analysis of the p50 subunit of NF-κB (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.