Research articleIGF-1 protects against Aβ25-35-induced neuronal cell death via inhibition of PUMA expression and Bax activation

- IGF-1 prevents Aβ25-35-induced cell death through the activation of PI3K/Akt pathway.
- IGF-1 mediated neuroprotection against Aβ25-35 toxicity via inhibition of PUMA expression.
- IGF-1 inhibits Aβ25-35-induced PUMA expression via the PI3K/Akt/FOXO3a Pathway.
- IGF-1 mediated neuroprotection against Aβ25-35 toxicity via inhibition of Bax activation.

Amyloid-β-peptide (Aβ) is considered to be the toxic species in AD and causes cell death in the affected areas of patient's brain. Insulin-like growth factor 1 (IGF-1) has been reported to attenuate Aβ toxicity in neuronal cells. However, the molecular mechanisms involved in the neuroprotective function of IGF-1 remain largely unknown. In the present study, we for the first time demonstrated that IGF-1 protects against Aβ-induced neurotoxicity via inhibition of PUMA expression and Bax activation. We found that IGF-1 could activate Akt, which in turn inhibited Aβ-induced FOXO3a nuclear translocation and thus decreased the binding ability of FOXO3a to PUMA promoter, leading to decreased PUMA expression. In addition, IGF-1 inhibited the translocation of Bax to the mitochondria induced by Aβ. Notably, addition of wortmannin, a specific inhibitor of PI3K, significantly abolished the neuroprotective effect of IGF-1, suggesting that IGF-1 exerts its anti-apoptotic effect depend on PI3K activity. Our findings may provide new insights into molecular mechanisms mediated by IGF-1 in cell survival against Aβ-induced apoptosis.