C-myb Plays an Essential Role in the Protective Function of IGF-1 on Cytotoxicity Induced by Aβ via the PI3K/Akt Pathway.

There have been numerous reports about neurodegenerative diseases, including Alzheimer's disease. Nevertheless, the molecules responsible for the neurodegeneration in Alzheimer's disease are basically unknown. Recent findings indicate that the cellular myeloblastosis (c-myb) regulates neural progenitor cell proliferation. In the current study, the function of insulin-like growth factor-1 (IGF-1) against cell toxicity in SH-SY5Y cells induced by β-amyloid 25-35 (Aβ) and its molecular mechanism were investigated. It was found that p25 protein production was raised by Aβ (25 μM), similar to the increased expression of μ-calpain. The results also showed that Aβ reduced c-myb, elevated tau hyper-phosphorylation, and induced death of SH-SY5Y cells. Loss of cell viability and apoptosis of SH-SY5Y cells induced by Aβ were attenuated by IGF-1 pretreatment in a dose-dependent manner. In addition, IGF-1 blocked μ-calpain expression, which was induced by Aβ and reduced p25 formation and tau hyper-phosphorylation. Moreover, the expression of c-myb in SH-SY5Y cells was increased by combining IGF-1 with Aβ or IGF-1 alone. The neuroprotective function of IGF-1 was attenuated in the SH-SY5Y cells, which were transfected with a c-myb small interfering RNA. Furthermore, LY294002, a specific PI3K inhibitor, reduced c-myb expression and abolished IGF-1's protective function in SH-SY5Y cell apoptosis induced by Aβ. The facts above indicate that c-myb has a role in IGF-1-mediated protection from Aβ-induced cytotoxicity via the PI3K/Akt pathway.