A JOURNAL OF NEUROLOGY Late-onset Parkinsonism in NFjB/c-Rel-deficient

Activation of the nuclear factor jB/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. Nigral degeneration was accompanied by a significant loss of dopa-minergic terminals and a significant reduction of dopamine and homovanillic acid levels in the striatum. Mice deficient of the c-Rel factor exhibited a marked immunoreactivity for fibrillary a-synuclein in the substantia nigra pars compacta as well as increased expression of divalent metal transporter 1 (DMT1) and iron staining in both the substantia nigra pars compacta and striatum. Aged c-rel/ mouse brain were characterized by increased microglial reactivity in the basal ganglia, but no astrocyti