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Aggregates of beta-amyloid peptide (betaAP), the main constituent of amyloid plaques in Alzheimer's brain, kill neurons by a not yet defined mechanism, leading to apoptotic death. Here, we report that both full-length betaAP((1-40)) or ((1-42)) and its active fragment betaAP((25-35)) act as proliferative signals for differentiated cortical neurons, driving(More)
Cell-cycle-related proteins, such as cyclins or cyclin-dependent kinases, are re-expressed in neurons committed to death in response to a variety of insults, including excitotoxins, hypoxia and ischemia, loss of trophic support, or beta-amyloid peptide. In some of these conditions events that are typical of the mid-G1 phase, such as cyclin-dependent kinase(More)
Cultured neurons exposed to synthetic beta-amyloid (Abeta) fragments reenter the cell cycle and initiate a pathway of DNA replication that involves the repair enzyme DNA polymerase-beta (DNA pol-beta) before undergoing apoptotic death. In this study, by performing coimmunoprecipitation experiments on cross-linked nucleoprotein fragments from Abeta-treated(More)
Beta-amyloid protein (betaAP) is thought to cause neuronal loss in Alzheimer's disease (AD). Applied to neurons in culture, betaAP induces neuronal death and hyperphosphorylation of tau protein, which forms neurofibrillary tangles (NFTs) in AD brains. Neurons also undergo rapid apoptotic death following reactivation of a mitotic cycle. However, the(More)
To investigate possible effects that may contribute, together with a direct action on neurohormone secretion, to the impairment of gonadal axis function during inflammation, we evaluated the effect of TNF alpha on the growth and viability of GT1-7 hypothalamic neurons and the intracellular transduction pathways involved in these effects. TNF alpha caused a(More)
The novel free radical scavenger and electron-trapping agent, idebenone, protects cultured cortical neurons against necrotic degeneration induced by either a brief exposure to N-methyl-D-aspartate (NMDA) or a prolonged exposure to kainate. As opposed to the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]- cyclohepten-5,10-imine hydrogen(More)
We investigated the expression and coupling to the phospholipase C signal transduction pathway of metabotropic glutamate receptor (mGluR) subtypes by Western blot analysis and agonist-stimulated inositol monophosphate formation in several brain regions of postnatal day 9 (P9) and adult rats. In the cerebral cortex, hippocampus, corpus striatum, olfactory(More)
The mechanism whereby a reactivation of cell cycle in neurons causes cell death is beginning to be identified. In cellular models of Alzheimer's disease, activation of a non-canonical pathway of DNA replication contributes to neuronal death. This pathway involves the repair enzyme DNA polymerase-beta, which is highly expressed in neurons of the Alzheimer's(More)
Thiazolidinedione rosiglitazone and 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), are two peroxisome proliferator-activated receptor (PPAR)-gamma ligands. The aim of this study was to investigate the effect of rosiglitazone and 15d-PGJ2 on the lung injury caused by bleomycin administration. Mice subjected to intratracheal administration of bleomycin(More)
Normal human lung fibroblasts downregulate the production of tumor necrosis factor (TNF)-alpha by activated monocytes through the production of prostaglandin E(2) (PGE(2)), contributing to the local control of the inflammatory process. In this study, we provide evidence that fibroblasts derived from diseased tissue, such as fibrotic lung fibroblasts,(More)