β-amyloid monomers are neuroprotective

Maria Laura Giuffrida, Filippo Caraci, Bruno Pignataro, Sebastiano Cataldo, Paolo De Bona, Valeria Bruno, Gemma Molinaro, Giuseppe Pappalardo, Angela Messina, Angelo Palmigiano, Domenico Garozzo, Ferdinando Nicoletti, Enrico Rizzarelli, Agata Copani

Research output: Contribution to journalArticle

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Abstract

The 42-aa-long β-amyloid protein - Aβ1-42 - isthought to play a central role in the pathogenesis of Alzheimer's disease (AD) (Walsh and Selkoe, 2007). Data from AD brain (Shankar et al., 2008), transgenic APP (amyloid precursor protein)-overexpressing mice (Lesne et al., 2006), and neuronal cultures treated with synthetic Aβpeptides (Lambert et al., 1998) indicate that self-association of Aβ1-42 monomers into soluble oligomers is required for neurotoxicity. The function of monomeric Aβ1-42 is unknown. The evidence that Aβ1-42 is present in the brain and CSF of normal individuals suggests that the peptide is physiologically active (Shoji, 2002). Here we show that synthetic Aβ1-42 monomers support the survival of developing neurons under conditions of trophic deprivation and protect mature neurons against excitotoxic death, a process that contributes to the overall neurodegeneration associated with AD. The neuroprotective action of Aβ1-42 monomers was mediated by the activation of the PI-3-K (phosphatidylinositol-3- kinase) pathway, and involved the stimulation of IGF-1 (insulin-like growth factor-1) receptors and/or other receptors of the insulin superfamily. Interestingly, monomers of Aβ1-42 carrying the Arctic mutation (E22G) associated with familiar AD (Nilsberth et al., 2001) were not neuroprotective. We suggest that pathological aggregation of Aβ1-42 may also cause neurodegeneration by depriving neurons of the protective activity of Aβ1-42 monomers. This "loss-of-function" hypothesis of neuronal death should be taken into consideration when designing therapies aimed at reducing Aβ burden.

Original languageEnglish (US)
Pages (from-to)10582-10587
Number of pages6
JournalJournal of Neuroscience
Volume29
Issue number34
DOIs
StatePublished - Aug 26 2009

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Amyloid
Alzheimer Disease
Neurons
Phosphatidylinositol 3-Kinase
Somatomedin Receptors
Amyloidogenic Proteins
Amyloid beta-Protein Precursor
Insulin Receptor
Brain
Peptides
Mutation
Therapeutics

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Giuffrida, M. L., Caraci, F., Pignataro, B., Cataldo, S., De Bona, P., Bruno, V., ... Copani, A. (2009). β-amyloid monomers are neuroprotective. Journal of Neuroscience, 29(34), 10582-10587. https://doi.org/10.1523/JNEUROSCI.1736-09.2009

β-amyloid monomers are neuroprotective. / Giuffrida, Maria Laura; Caraci, Filippo; Pignataro, Bruno; Cataldo, Sebastiano; De Bona, Paolo; Bruno, Valeria; Molinaro, Gemma; Pappalardo, Giuseppe; Messina, Angela; Palmigiano, Angelo; Garozzo, Domenico; Nicoletti, Ferdinando; Rizzarelli, Enrico; Copani, Agata.

In: Journal of Neuroscience, Vol. 29, No. 34, 26.08.2009, p. 10582-10587.

Research output: Contribution to journalArticle

Giuffrida, ML, Caraci, F, Pignataro, B, Cataldo, S, De Bona, P, Bruno, V, Molinaro, G, Pappalardo, G, Messina, A, Palmigiano, A, Garozzo, D, Nicoletti, F, Rizzarelli, E & Copani, A 2009, 'β-amyloid monomers are neuroprotective', Journal of Neuroscience, vol. 29, no. 34, pp. 10582-10587. https://doi.org/10.1523/JNEUROSCI.1736-09.2009
Giuffrida ML, Caraci F, Pignataro B, Cataldo S, De Bona P, Bruno V et al. β-amyloid monomers are neuroprotective. Journal of Neuroscience. 2009 Aug 26;29(34):10582-10587. https://doi.org/10.1523/JNEUROSCI.1736-09.2009
Giuffrida, Maria Laura ; Caraci, Filippo ; Pignataro, Bruno ; Cataldo, Sebastiano ; De Bona, Paolo ; Bruno, Valeria ; Molinaro, Gemma ; Pappalardo, Giuseppe ; Messina, Angela ; Palmigiano, Angelo ; Garozzo, Domenico ; Nicoletti, Ferdinando ; Rizzarelli, Enrico ; Copani, Agata. / β-amyloid monomers are neuroprotective. In: Journal of Neuroscience. 2009 ; Vol. 29, No. 34. pp. 10582-10587.
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AU - Pappalardo, Giuseppe

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AU - Rizzarelli, Enrico

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