Disentangling the signaling complexity of nerve growth factor receptors by CRISPR/Cas9.

The binding of nerve growth factor (NGF) to the tropomyosin-related kinase A (TrkA) and p75 receptors activates a large variety of pathways regulating critical processes as diverse as proliferation, differentiation, membrane potential, synaptic plasticity, and pain. To ascertain the details of TrkA-p75 interaction and cooperation, a plethora of experiments, mostly based on receptor overexpression or downregulation, have been performed. Among the heterogeneous cellular systems used for studying NGF signaling, the PC12 pheochromocytoma-derived cell line is a widely used model.

Zika virus induces FOXG1 nuclear displacement and downregulation in human neural progenitors.

Congenital alterations in the levels of the transcription factor Forkhead box g1 (FOXG1) coding gene trigger "FOXG1 syndrome," a spectrum that recapitulates birth defects found in the "congenital Zika syndrome," such as microcephaly and other neurodevelopmental conditions. Here, we report that Zika virus (ZIKV) infection alters FOXG1 nuclear localization and causes its downregulation, thus impairing expression of genes involved in cell replication and apoptosis in several cell models, including human neural progenitor cells. Growth factors, such as EGF and FGF2, and Thr271 residue located in FOXG1 AKT domain, take part in the nuclear displacement and apoptosis protection, respectively.

Gene Expression of Disease-related Genes in Alzheimer's Disease is Impaired by Tau Aggregation.

Neuronal hyperexcitability linked to an increase in glutamate signalling is a peculiar trait of the early stages of Alzheimer's disease (AD) and tauopathies, however, a progressive reduction in glutamate release follows in advanced stages. We recently reported that in the early phases of the neurodegenerative process, soluble, non-aggregated Tau accumulates in the nucleus and modulates the expression of disease-relevant genes directly involved in glutamatergic transmission, thus establishing a link between Tau instability and altered neurotransmission. Here we report that while the nuclear translocation of Tau in cultured cells is not impaired by its own aggregation, the nuclear amyloid inclusions of aggregated Tau abolish Tau-dependent increased expression of the glutamate transporter.

The NGF Mutation Specifically Impairs Nociception without Affecting Cognitive Performance in a Mouse Model of Hereditary Sensory and Autonomic Neuropathy Type V.

Nerve growth factor (NGF) is a key mediator of nociception, acting during the development and differentiation of dorsal root ganglion (DRG) neurons, and on adult DRG neuron sensitization to painful stimuli. NGF also has central actions in the brain, where it regulates the phenotypic maintenance of cholinergic neurons. The physiological function of NGF as a pain mediator is altered in patients with Hereditary Sensory and Autonomic Neuropathy type V (HSAN V), caused by the 661C>T transition in the gene, resulting in the R100W missense mutation in mature NGF.

Cortical Seizures in Mice are Accompanied by Akt/S6 Overactivation, Excitation/Inhibition Imbalance and Impaired Synaptic Transmission.

The correct morphofunctional shaping of the cerebral cortex requires a continuous interaction between intrinsic (genes/molecules expressed within the tissue) and extrinsic (e.g., neural activity) factors at all developmental stages.