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Neurobiol Aging. 2014 Jun;35(6):1301-8. doi: 10.1016/j.neurobiolaging.2014.01.002. Epub 2014 Jan 10.

Monomeric Aβ1-42 and RAGE: key players in neuronal differentiation.

Author information

  • 1Department of Experimental Medicine, University of Genoa, Genoa, Italy.
  • 2Department of Internal Medicine and Medical Specialities, University of Genoa, Genoa, Italy; IRCCS Azienda Ospedaliera Universitaria San Martino-IST, Istituto Nazionale Ricerca sul Cancro, Genoa, Italy.
  • 3Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy.
  • 4Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
  • 5Department of Internal Medicine and Medical Specialities, University of Genoa, Genoa, Italy.
  • 6Department of Experimental Medicine, University of Genoa, Genoa, Italy. Electronic address: mariapaola.nitti@unige.it.

Abstract

The aggregation of amyloid-β (Aβ) peptides plays a crucial role in the onset and progression of Alzheimer's disease. Monomeric form of Aβ, indeed, could exert a physiological role. Considering the anti-oligomerization property of all-trans retinoic acid (ATRA), the involvement of monomeric Aβ1-42 in ATRA-induced neuronal differentiation has been investigated. Four-day ATRA treatment increases β-secretase 1 (BACE1) level, Aβ1-42 production, and receptor for advanced glycation end-products (RAGE) expression. RAGE is a well-recognized receptor for Aβ, and the block of both RAGE and Aβ1-42 with specific antibodies strongly impairs neurite formation in ATRA-treated cells. The involvement of Aβ1-42 and RAGE in ATRA-induced morphologic changes has been confirmed treating undifferentiated cells with different molecular assemblies of peptide: 1 μM monomeric, but not oligomeric, Aβ1-42 increases RAGE expression and favors neurite elongation. The block of RAGE completely prevents this effect. Furthermore, our data underline the involvement of the RAGE-dependent adhesion molecule amphoterin-induced gene and open reading frame-1 as downstream effector of both ATRA and Aβ1-42. In conclusion, our findings identify a novel physiological role for monomeric Aβ1-42 and RAGE in neuronal differentiation.

Copyright © 2014 Elsevier Inc. All rights reserved.

KEYWORDS:

AMIGO-1; Aβ peptide molecular assembly; Aβ1–42; RAGE; Retinoic acid

PMID:
24484607
[PubMed - indexed for MEDLINE]
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