Involvement of notch signaling pathway in amyloid precursor protein induced glial differentiation

The amyloid precursor protein (APP) has been mainly studied in its role in the production of amyloid beta peptides (A beta) because A beta deposition is a hallmark of Alzheimer s disease Although several studies suggest APP has physiological functions it is still controversial We previously reported that APP increased glial differentiation of neural progenitor cells (NPCs) In the current study NPCs transplanted into APP23 transgenic mice primarily differentiated Into glial cells In vitro treatment with secreted APP (sAPP) dose-dependently increased glial fibrillary acidic protein (GFAP) immuno-positive cells in NPCs and over expression of APP caused most NPCs to differentiate into GFAP immuno-positive cells Treatment with sAPP also dose-dependently increased expression levels of GFAP in NT-2/D1 cells along with the generation of Notch intracellular domain (NICD) and expression of Hairy and enhancer of split 1 (Hes1) Treatment with gamma-secretase inhibitor suppressed the generation of NICD and reduced Hes1 and GFAP expressions Treatment with the N-terminal domain of APP (APP 1-205) was enough to induce up regulation of GFAP and Hes1 expressions and application of 22 C11 antibodies recognizing N-terminal APP suppressed these changes by sAPP These results indicate APP Induces glial differentiation of NPCs through Notch signaling (C) 2010 Elsevier B V All rights reserved