IGF-1 alleviates NMDA-induced excitotoxicity in cultured hippocampal neurons against autophagy via the NR2B/PI3K-AKT-mTOR pathway.

Insulin-like growth factor-1 (IGF-1) is a brain-specific multifunctional protein involved in neuronal polarity and axonal guidance. Mature IGF-1 triggers three enzymes, mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase (PI3K), and phosphoinositide phospholipase C-γ (PLC-γ), which are its predominant downstream regulators. The PI3K-AKT signaling pathway is upstream of the mammalian target of rapamycin (mTOR), which is of great importance in the induction of autophagy. However, whether the neuroprotective effect of IGF-1 against excitotoxicity is mediated by autophagy through the PI3K/AKT/mTOR pathway remains to be elucidated. The induction of autophagy following NMDA treatment was determined by microtubule-associated protein light chain 3 (LC3) conversion and the result of this autophagy was assessed by monitoring the cleavage of caspase 3 in cultured hippocampal neurons. Cell viability was determined using MTT and LDH assay, and PI-staining was used to estimate the fate of autophagy and the protective effect of IGF-1. In addition, IGF-1 was found to decrease autophagy induced by NMDA using transmission electron microscopy and MDC staining. The protective effect of IGF-1 against autophagy was accompanied with up-regulation of phospho-AKT (p-AKT) and phospho-mTOR (p-mTOR), which was blocked by the inhibitor of PI3K. At the same time, the activation of NR2B resulting in the down-regulation of p-AKT and p-mTOR was blocked by IGF-1. Together, these data suggest that NMDA induces the autophagy, followed by apoptosis in cultured hippocampal neurons, and that IGF-1 can block this effect via inhibition of NR2B receptors and activation of the PI3K-AKT-mTOR pathway.

Wang Y ，Wang W ，Li D ，Li M ，Wang P ，Wen J ，Liang M ，Su B ，Yin Y ... -  《-》

IGF-1-Involved Negative Feedback of NR2B NMDA Subunits Protects Cultured Hippocampal Neurons Against NMDA-Induced Excitotoxicity.

Li Y ，Sun W ，Han S ，Li J ，Ding S ，Wang W ，Yin Y ... -  《-》

Neuroprotective effect of brain-derived neurotrophic factor mediated by autophagy through the PI3K/Akt/mTOR pathway.

Chen A ，Xiong LJ ，Tong Y ，Mao M ... -  《-》

Puquitinib mesylate (XC-302) induces autophagy via inhibiting the PI3K/AKT/mTOR signaling pathway in nasopharyngeal cancer cells.

Wang KF ，Yang H ，Jiang WQ ，Li S ，Cai YC ... -  《-》

Schizandrol A protects against Aβ(1-42)-induced autophagy via activation of PI3K/AKT/mTOR pathway in SH-SY5Y cells and primary hippocampal neurons.

Song L ，Yao L ，Zhang L ，Piao Z ，Lu Y ... -  《-》