| First Author | Aulston BD | Year | 2018 |
| Journal | Exp Neurol | Volume | 303 |
| Pages | 29-37 | PubMed ID | 29410317 |
| Mgi Jnum | J:261137 | Mgi Id | MGI:6153056 |
| Doi | 10.1016/j.expneurol.2018.01.013 | Citation | Aulston BD, et al. (2018) Secreted amyloid precursor protein alpha activates neuronal insulin receptors and prevents diabetes-induced encephalopathy. Exp Neurol 303:29-37 |
| abstractText | Secreted amyloid precursor protein alpha (sAPPalpha) is a potent neurotrophin in the CNS but a dedicated receptor has not been found. However, protein interactions involving amyloid beta (Abeta), a peptide cleaved from the same parent peptide as sAPPalpha, indicate that insulin receptors (IRs) could be a target of amyloid peptides. In this study, in vitro analysis of cortical neuronal cultures revealed that exogenous sAPPalpha increased IR phosphorylation in the absence of insulin. Furthermore, in an APP overexpressing mouse model, sAPPalpha bound IRs in the cortex with significantly greater binding in hypoinsulinemic animals. To further examine the effects of sAPPalpha on the diabetic brain, we next rendered sAPPalpha overexpressing mice insulin depleted and found that sAPPalpha blocked aberrant tau phosphorylation (T231) in cortical tissue after 16weeks diabetes. sAPPalpha overexpression also prevented hyperphosphorylation of AKT/GSK3 and activation of the unfolded protein response (UPR). In total, these data show sAPPalpha binds and activates neuronal IRs and that sAPPalpha has a protective effect on diabetic brain tissue. |
