Inhibiting p53 pathways in microglia attenuates microglial‐evoked neurotoxicity following exposure to Alzheimer peptides

• DOI: 10.1111/j.1471-4159.2009.06485.x
• Publication Date: 2009-11-06T14:13:40Z
• Authors: Christopher M. Da...; Ioanna G. Sevastou; Claudie Hooper; Jennifer M. Pocock
• Keywords: Neurotoxicity; Neuroglia

Microglial activation can lead to microglial apoptosis, which may serve remove highly reactive and possibly neurotoxic microglia. However the loss of microglia have consequences for future recovery, protection repair. P53, a nuclear phosphoprotein transcription factor, is critical activating expression genes involved in cell-cycle arrest stress-induced apoptosis. In neurodegenerative diseases p53 significantly increased glial cells, numbers fall. Following with chromogranin A (100 nM), or beta-amyloid(25-35), (10 microM), became apoptotic. Furthermore, was enhanced, peaking at 4-6 h after exposure activators. The inhibitor, pifithrin-alpha, microM) reduced modulated levels apoptosis induced by activation. Lithium chloride (5 mM), modulate p53-mediated pathways, also suggesting glycogen synthase kinase-3 plays role. Regulating pathways inducible nitric oxide tumour necrosis factor alpha secretion. Inhibiting mediated prevented neurotoxicity targeting therapeutic benefit Alzheimer's disease.