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

    Authors

    Y. D. Kwak; A. Marutle; E. Dantuma; S. Merchant; S. Bushnev;K. Sugaya

    Comments

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    Abbreviated Journal Title

    Eur. J. Pharmacol.

    Keywords

    Alzheimer s disease; Amyloid precursor protein; Notch; Glial; differentiation; Neural progenitor cells; NEURAL STEM-CELLS; EMBRYONAL CARCINOMA-CELLS; CENTRAL-NERVOUS-SYSTEM; ALZHEIMERS-DISEASE; DOWNS-SYNDROME; GENE-EXPRESSION; APP; GROWTH; DOMAIN; PROLIFERATION; Pharmacology & Pharmacy

    Abstract

    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

    Journal Title

    European Journal of Pharmacology

    Volume

    650

    Issue/Number

    1

    Publication Date

    1-1-2011

    Document Type

    Article

    Language

    English

    First Page

    18

    Last Page

    27

    WOS Identifier

    WOS:000285893800003

    ISSN

    0014-2999

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