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

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

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.

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

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alzheimer Disease / genetics*
  • Alzheimer Disease / pathology*
  • Amyloid Precursor Protein Secretases / metabolism
  • Amyloid Precursor Protein Secretases / physiology
  • Amyloid beta-Peptides / chemistry*
  • Amyloid beta-Peptides / immunology
  • Amyloid beta-Peptides / metabolism
  • Amyloid beta-Peptides / physiology*
  • Antibodies / pharmacology
  • Aspartic Acid Endopeptidases / metabolism
  • Aspartic Acid Endopeptidases / physiology
  • Cell Differentiation / drug effects
  • Cell Differentiation / genetics*
  • Disease Progression
  • Humans
  • Membrane Glycoproteins / genetics
  • Membrane Glycoproteins / physiology
  • Nerve Tissue Proteins / genetics
  • Nerve Tissue Proteins / physiology
  • Neurites / physiology
  • Neurons / cytology*
  • Neurons / physiology
  • Open Reading Frames
  • Peptide Fragments / chemistry*
  • Peptide Fragments / immunology
  • Peptide Fragments / metabolism
  • Peptide Fragments / physiology*
  • Polymerization / drug effects
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic / immunology
  • Receptors, Immunologic / metabolism
  • Receptors, Immunologic / physiology*
  • Tretinoin / pharmacology
  • Tumor Cells, Cultured
  • Up-Regulation / drug effects
  • Up-Regulation / physiology

Substances

  • AMIGO1 protein, human
  • Amyloid beta-Peptides
  • Antibodies
  • Membrane Glycoproteins
  • Nerve Tissue Proteins
  • Peptide Fragments
  • Receptor for Advanced Glycation End Products
  • Receptors, Immunologic
  • amyloid beta-protein (1-42)
  • Tretinoin
  • Amyloid Precursor Protein Secretases
  • Aspartic Acid Endopeptidases
  • BACE1 protein, human