C-myb Plays an Essential Role in the Protective Function of IGF-1 on Cytotoxicity Induced by Aβ25–35 via the PI3K/Akt Pathway

Abstract

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.

Implications of PI3K/AKT/PTEN Signaling on Superoxide Dismutases Expression and in the Pathogenesis of Alzheimer’s Disease

“…For example, a study has suggested that PI3K/AKT signaling is attenuated in the brains of AD patients [ 74 ]. Moreover, PI3K/AKT inhibitor upsurges tau hyperphosphorylation [ 75 ].…”

High Expression of Nicotinamide N-Methyltransferase in Patients with Sporadic Alzheimer’s Disease

“…Akt is a cell survival kinase whose dysregulation is reported in neurodegenerative diseases such as PD and AD [63,64]. Akt phosphorylation of downstream targets regulates a variety of cellular processes, one of which is glycogen synthase kinase-3β (GSK-3β), which phosphorylates tau [65]. The Akt pathway is downregulated in AD [66], leading to the overactivity of GSK-3β which, in turn, results in the hyperphosphorylation of tau [67].…”

Meta-Analysis of Gene Expression Changes in the Blood of Patients with Mild Cognitive Impairment and Alzheimer’s Disease Dementia

“…The transcription factor SRF was identified as a key regulator in ADD pathology [65]. The transcription factors MYB and MEF2A were respectively involved in protection for Aβ toxicity and in neuronal survival [118,119].…”