Title

Secreted Type Of Amyloid Precursor Protein Induces Glial Differentiation By Stimulating The Bmp/Smad Signaling Pathway

Keywords

Alzheimer's disease; Amyloid precursor protein; BMP/Smad signaling pathway; Down syndrome; Glial differentiation; Stem cell therapy

Abstract

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases leading to dementia. Although cytotoxicity of amyloid β peptides has been intensively studied within pathophysiology of AD, the physiological function of amyloid precursor protein (APP) still remains unclarified. We have shown previously that secreted APPα (sAPPα) is associated with glial differentiation of neural stem cells. To elucidate specific mechanisms underlying sAPPα-induced gliogenesis, we examined the potential involvement of bone morphogenic proteins (BMPs). BMPs are one of the factors involved in glial differentiation of neural progenitor cells. When expressions of BMP-2, -4, and -7 were examined, upregulation of BMP-4 expression was solely observed as a result of treatment with sAPPα in a time and dose-dependent manner. Furthermore, the treatment of sAPPα promoted phosphorylation of Smad1/5/8, a downstream signaling mediator of BMP receptors. Interestingly, N-terminal domain of APP (1-205) was sufficient to elevate BMP4 expression, resulting in an increase of glial fibrillary acidic protein (GFAP) expression and phosphorylation of Smad1/5/8. However, the application of APP neutralizing antibody and anti-BMP4 antibody significantly suppressed expression of BMP-4 as well as phosphorylation of Smad1/5/8. Thus, our results indicate that sAPPα-induced gliogenesis is in part mediated by the BMP-4 signaling pathway. We also observed upregulation of BMP-4 and phosphorylation of Smad1/5/8 in APP transgenic mice. It is imperative to unravel the mechanisms underlying the role of BMP-4 during APPα-induced glial differentiation in hope of providing novel prevention or treatment for AD. © 2014 Elsevier Inc.

Publication Date

5-9-2014

Publication Title

Biochemical and Biophysical Research Communications

Volume

447

Issue

3

Number of Pages

394-399

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1016/j.bbrc.2014.03.139

Socpus ID

84900298588 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/84900298588

This document is currently not available here.

Share

COinS