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.

Glutamatergic neurons induce expression of functional glutamatergic synapses in primary myotubes.

Background: The functioning of the nervous system depends upon the specificity of its synaptic contacts. The mechanisms triggering the expression of the appropriate receptors on postsynaptic membrane and the role of the presynaptic partner in the differentiation of postsynaptic structures are little known.

Methods And Findings: To address these questions we cocultured murine primary muscle cells with several glutamatergic neurons, either cortical, cerebellar or hippocampal.

The γ-secretase modulator CHF5074 reduces the accumulation of native hyperphosphorylated tau in a transgenic mouse model of Alzheimer's disease.

The relationship between β-amyloid (Aβ) and tau is not fully understood, though it is proposed that in the pathogenesis of Alzheimer's disease (AD) Aβ accumulation precedes and promotes tau hyperphosphorylation via activation of glycogen synthase kinase-3beta (GSK-3β). Both events contribute to learning and memory impairments. Modulation of γ-secretase activity has proved to reduce the Aβ burden and cognitive deficits in mouse models of AD, but its ability in reducing the tau pathology remains elusive.

Glutamatergic reinnervation and assembly of glutamatergic synapses in adult rat skeletal muscle occurs at cholinergic endplates.

After denervation of adult rat abdominal muscles, the postsynaptic apparatus of neuromuscular junctions (NMJs) retains its original architecture and clustering of acetylcholine receptors (AChRs). When descending fibers of the spinal cord are surgically diverted to this muscle by a nerve grafting procedure, supraspinal glutamatergic neurons can innervate muscle fibers and restore motor function; the newly formed NMJs switch from a cholinergic to a glutamatergic-type synapse. We show here that regenerating nerve endings contact the fibers in an area occupied by cholinergic endplates.

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.