Late-onset Parkinsonism in NFκB/c-Rel-deficient mice.

Activation of the nuclear factor κB/c-Rel can increase neuronal resilience to pathological noxae by regulating the expression of pro-survival manganese superoxide dismutase (MnSOD, now known as SOD2) and Bcl-xL genes. We show here that c-Rel-deficient (c-rel(-/-)) mice developed a Parkinson's disease-like neuropathology with ageing. At 18 months of age, c-rel(-/-) mice exhibited a significant loss of dopaminergic neurons in the substantia nigra pars compacta, as assessed by tyrosine hydroxylase-immunoreactivity and Nissl staining.

NF-kappaB dimers in the regulation of neuronal survival.

Nuclear factor-kappaB (NF-kappaB) is a dimeric transcription factor composed of five members, p50, RelA/p65, c-Rel, RelB, and p52 that can diversely combine to form the active transcriptional dimer. NF-kappaB controls the expression of genes that regulate a broad range of biological processes in the central nervous system such as synaptic plasticity, neurogenesis, and differentiation. Although NF-kappaB is essential for neuron survival and its activation may protect neurons against oxidative-stresses or ischemia-induced neurodegeneration, NF-kappaB activation can contribute to inflammatory reactions and apoptotic cell death after brain injury and stroke.

NF-kappaB p50/RelA and c-Rel-containing dimers: opposite regulators of neuron vulnerability to ischaemia.

Diverse nuclear factor-kappaB subunits mediate opposite effects of extracellular signals on neuron survival. While RelA is activated by neurotoxic agents, c-Rel drives neuroprotective effects. In brain ischaemia RelA and p50 factors rapidly activate, but how they associate with c-Rel to form active dimers and contribute to the changes in diverse dimer activation for neuron susceptibility is unknown.