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

Sabrina Piras, Anna L. Furfaro, Alessandra Piccini, Mario Passalacqua, Roberta Borghi, Enrico Carminati, Alessia Parodi, Laura Colombo, Mario Salmona, Maria A. Pronzato, Umberto M. Marinari, Massimo Tabaton, Mariapaola Nitti

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1301-1308
Number of pages8
JournalNeurobiology of Aging
Volume35
Issue number6
DOIs
Publication statusPublished - Jun 2014

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Keywords

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

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)
  • Ageing
  • Developmental Biology
  • Geriatrics and Gerontology
  • Medicine(all)

Cite this

Piras, S., Furfaro, A. L., Piccini, A., Passalacqua, M., Borghi, R., Carminati, E., Parodi, A., Colombo, L., Salmona, M., Pronzato, M. A., Marinari, U. M., Tabaton, M., & Nitti, M. (2014). Monomeric Aβ1-42 and RAGE: Key players in neuronal differentiation. Neurobiology of Aging, 35(6), 1301-1308. https://doi.org/10.1016/j.neurobiolaging.2014.01.002