Monomeric Aβ1-42 and RAGE: key players in neuronal differentiation.
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.
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Sabrina
S
Piras
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Anna L
AL
Furfaro
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Alessandra
A
Piccini
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Mario
M
Passalacqua
Department 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.
Roberta
R
Borghi
Department 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.
Enrico
E
Carminati
Center of Excellence for Biomedical Research (CEBR), University of Genoa, Genoa, Italy.
Alessia
A
Parodi
Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
Laura
L
Colombo
Department of Molecular Biochemistry and Pharmacology, IRCCS-Istituto di Ricerche Farmacologiche "Mario Negri", Milano, Italy.
Mario
M
Salmona
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Maria A
MA
Pronzato
Department of Experimental Medicine, University of Genoa, Genoa, Italy.
Umberto M
UM
Marinari
Department of Internal Medicine and Medical Specialities, University of Genoa, Genoa, Italy.
Massimo
M
Tabaton
Department of Experimental Medicine, University of Genoa, Genoa, Italy. Electronic address: mariapaola.nitti@unige.it.
Mariapaola
M
Nitti
D000544:Alzheimer Disease / Q000235:genetics* / Q000473:pathology*; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism / Q000502:physiology; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D000906:Antibodies / Q000494:pharmacology; D016282:Aspartic Acid Endopeptidases / Q000378:metabolism / Q000502:physiology; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D018450:Disease Progression; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000502:physiology; D016501:Neurites / Q000502:physiology; D009474:Neurons / Q000166:cytology* / Q000502:physiology; D016366:Open Reading Frames; D010446:Peptide Fragments / Q000737:chemistry* / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D058105:Polymerization / Q000187:drug effects; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000276:immunology / Q000378:metabolism / Q000502:physiology*; D014212:Tretinoin / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
C571087:AMIGO1 protein, human; D016229:Amyloid beta-Peptides; D000906:Antibodies; D008562:Membrane Glycoproteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; C075222:amyloid beta-protein (1-42); D014212:Tretinoin; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
AMIGO-1; Aβ peptide molecular assembly; Aβ1–42; RAGE; Retinoic acid