Title

Involvement Of Notch Signaling Pathway In Amyloid Precursor Protein Induced Glial Differentiation

Keywords

Alzheimer's disease; Amyloid precursor protein; Glial differentiation; Neural progenitor cells; Notch

Abstract

The amyloid precursor protein (APP) has been mainly studied in its role in the production of amyloid β peptides (Aβ), because Aβ 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 γ-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. © 2010 Elsevier B.V. All rights reserved.

Publication Date

1-10-2011

Publication Title

European Journal of Pharmacology

Volume

650

Issue

1

Number of Pages

18-27

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.ejphar.2010.09.015

Socpus ID

78649759353 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/78649759353

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