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Beta-Amyloid Monomer and Insulin/IGF-1 Signaling in Alzheimer's Disease

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Abstract

Alzheimer's disease is the most common form of dementia among older people and is still untreatable. While β-amyloid protein is recognized as the disease determinant with a pivotal role in inducing neuronal loss and dementia, an impaired brain insulin signaling seems to account in part for the cognitive deficit associated with the disease. The origin of this defective signaling is uncertain. Accumulating toxic species of β-amyloid, the so-called oligomers, has been proposed to be responsible for downregulation of neuronal insulin receptors. We have found that the nontoxic form of β-amyloid, the monomer, is able to activate insulin/insulin-like growth factor-1 (IGF-1) receptor signaling and thus behaves as a neuroprotectant agent. Our suggestion is that depletion of β-amyloid monomers, occurring in the preclinical phase of Alzheimer's disease, might be the cause of early insulin/IGF-1 signaling disturbances that anticipate cognitive decline.

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Acknowledgments

We acknowledge the source of funding that helped to support the writing of this article. The source is as follows: PRIN 2009 by the Italian Ministry of University and Research to A.C. The authors thank Dr. Giuseppe Pappalardo (CNR-IBB, Catania) for the helpful discussions on structural features and properties of β-amyloid.

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Authors and Affiliations

  1. Institute of Biostructure and Bioimaging, National Research Council, Viale Andrea Doria, Catania, 95125, Italy

    Maria Laura Giuffrida & Agata Copani

  2. PhD Program in Neuropharmacology, University of Catania, Viale Andrea Doria, Catania, 95125, Italy

    Flora Tomasello

  3. Department of Formative Processes, University of Catania, Via Biblioteca 2, Catania, 95100, Italy

    Filippo Caraci

  4. Department of Drug Sciences, University of Catania, Viale Andrea Doria, Catania, 95125, Italy

    Santina Chiechio & Agata Copani

  5. Department of Human Physiology and Pharmacology, University of Rome “La Sapienza”, Piazzale Aldo Moro, Rome, 00185, Italy

    Ferdinando Nicoletti

  6. Instituto Neurologico Mediterraneo, Neuromed, Località Camerelle, Pozzilli, 86077, Italy

    Ferdinando Nicoletti

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  1. Maria Laura Giuffrida
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  2. Flora Tomasello
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  3. Filippo Caraci
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  6. Agata Copani
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Correspondence to Ferdinando Nicoletti or Agata Copani.

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Giuffrida, M.L., Tomasello, F., Caraci, F. et al. Beta-Amyloid Monomer and Insulin/IGF-1 Signaling in Alzheimer's Disease. Mol Neurobiol 46, 605–613 (2012). https://doi.org/10.1007/s12035-012-8313-6

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