Neuroreport · 2004 · 51 citations · 15 references
Life SciencesNeurosciencePharmacologyApoptosisMolecular NeuroscienceNeuropharmacologyAlzheimer DiseaseApoptosis In NeurodegenerationNeurodegenerative DiseasesNeurodegenerative DisordersNeuronal Cell DeathNeuroprotectionAlzheimer Disease NeuroprotectionAmyloid-beta Induced ApoptosisAmyloid-beta-induced NeurotoxicityMek InhibitionMek InhibitorsMek SignalingPi3k InhibitorsPi3k Signaling
Apoptosis is implicated in the pathophysiology of Alzheimer's disease. Extracellular guanosine inhibits staurosporine-induced apoptosis in astrocytes. We examined whether guanosine protects SH-SY5Y human neuroblastoma cells against beta-amyloid(betaA)-induced apoptosis. Addition of betaA (fragment 25-35, 5 microM for 24 h) to SH-SY5Y cells increased the number of apoptotic cells, as evaluated by oligonucleosome ELISA. Guanosine pre-treatment decreased betaA-induced apoptosis (maximal effect after 24 h, 300 microM, p<0.05). The anti-apoptotic effect of guanosine was reduced by LY294002 (PI3K inhibitor) or PD98059 (MEK inhibitor) (p<0.05). Guanosine increased phosphorylation of Akt/PKB, and this was abolished by inhibiting PI3K or MEK, (p<0.001, 5 min). Thus, the protective effect of guanosine against betaA-induced apoptosis of SH-SY5Y cells is mediated via activation of the PI3K/Akt/PKB and MAPK pathways.
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Caspase-12 mediates endoplasmic-reticulum-specific apoptosis and cytotoxicity by amyloid-β
Toshiyuki Nakagawa, Hong Zhu, Nobuhiro Morishima et al. · Nature · 2000 · 3.3K citations