title: Monomeric ß-amyloid interacts with type-1 insulin-like growth factor receptors to provide energy supply to neurons.
abstract: ß-amyloid (Aß1-42) is produced by proteolytic cleavage of the transmembrane type-1 protein, amyloid precursor protein. Under pathological conditions, Aß1-42self-aggregates into oligomers, which cause synaptic dysfunction and neuronal loss, and are considered the culprit of Alzheimer's disease (AD). However, Aß1-42 is mainly monomeric at physiological concentrations, and the precise role of monomeric Aß1-42 in neuronal function is largely unknown. We report that the monomer of Aß1-42 activates type-1 insulin-like growth factor receptors and enhances glucose uptake in neurons and peripheral cells by promoting the translocation of the Glut3 glucose transporter from the cytosol to the plasma membrane. In neurons, activity-dependent glucose uptake was blunted after blocking endogenous Aß production, and re-established in the presence of cerebrospinal fluid Aß. APP-null neurons failed to enhance depolarization-stimulated glucose uptake unless exogenous monomeric Aß1-42 was added. These data suggest that Aß1-42 monomers were critical for maintaining neuronal glucose homeostasis. Accordingly, exogenous Aß1-42 monomers were able to rescue the low levels of glucose consumption observed in brain slices from AD mutant mice.
authors: National Research Council, Institute of Biostructure and Bioimaging Catania, Italy.
authors: Maria L
authors: ML
authors: Giuffrida
authors: National Research Council, Institute of Biostructure and Bioimaging Catania, Italy ; PhD Program in Neuropharmacology, University of Catania Catania, Italy.
authors: Marianna F
authors: MF
authors: Tomasello
authors: National Research Council, Institute of Biostructure and Bioimaging Catania, Italy ; Department of Clinical and Molecular Biomedicine, University of Catania Catania, Italy.
authors: Giuseppe
authors: G
authors: Pandini
authors: Department of Drug Sciences, University of Catania Catania, Italy ; IRCCS Associazione Oasi Maria S.S., Institute for Research on Mental Retardation and Brain Aging Troina, Italy.
authors: Filippo
authors: F
authors: Caraci
authors: Department of Molecular Pathology, Neuropharmacology Unit, IRCCS Neuromed Pozzilli, Italy.
authors: Giuseppe
authors: G
authors: Battaglia
authors: Department of Molecular Pathology, Neuropharmacology Unit, IRCCS Neuromed Pozzilli, Italy.
authors: Carla
authors: C
authors: Busceti
authors: Department of Molecular Pathology, Neuropharmacology Unit, IRCCS Neuromed Pozzilli, Italy.
authors: Paola
authors: P
authors: Di Pietro
authors: National Research Council, Institute of Biostructure and Bioimaging Catania, Italy.
authors: Giuseppe
authors: G
authors: Pappalardo
authors: National Research Council, Institute of Biostructure and Bioimaging Catania, Italy.
authors: Francesco
authors: F
authors: Attanasio
authors: Department of Drug Sciences, University of Catania Catania, Italy.
authors: Santina
authors: S
authors: Chiechio
authors: NEUROFARBA, University of Florence Florence, Italy.
authors: Silvia
authors: S
authors: Bagnoli
authors: NEUROFARBA, University of Florence Florence, Italy.
authors: Benedetta
authors: B
authors: Nacmias
authors: NEUROFARBA, University of Florence Florence, Italy.
authors: Sandro
authors: S
authors: Sorbi
authors: National Research Council, Institute of Biostructure and Bioimaging Catania, Italy ; Department of Clinical and Molecular Biomedicine, University of Catania Catania, Italy.
authors: Riccardo
authors: R
authors: Vigneri
authors: National Research Council, Institute of Biostructure and Bioimaging Catania, Italy.
authors: Enrico
authors: E
authors: Rizzarelli
authors: Department of Molecular Pathology, Neuropharmacology Unit, IRCCS Neuromed Pozzilli, Italy ; Department of Human Physiology and Pharmacology, University "La Sapienza" Rome, Italy.
authors: Ferdinando
authors: F
authors: Nicoletti
authors: National Research Council, Institute of Biostructure and Bioimaging Catania, Italy ; Department of Drug Sciences, University of Catania Catania, Italy.
authors: Agata
authors: A
authors: Copani
keywords: Alzheimer's disease; Glut3; IGF-IR; glucose; ß-amyloid