In a comprehensive proteomics study aiming at the identification of proteins associated with amyloid-beta (Aβ)-mediated toxicity in cultured cortical neurons, we have identified Thimet oligopeptidase (THOP1). Functional modulation of THOP1 levels in primary cortical neurons demonstrated that its overexpression was neuroprotective against Aβ toxicity, while RNAi knockdown made neurons more vulnerable to amyloid peptide. In the TgCRND8 transgenic mouse model of amyloid plaque deposition, an age-dependent increase of THOP1 expression was found in brain tissue, where it co-localized with Aβ plaques. In accordance with these findings, THOP1 expression was significantly increased in human AD brain tissue as compared to nondemented controls. These results provide compelling evidence for a neuroprotective role of THOP1 against toxic effects of Aβ in the early stages of AD pathology, and suggest that the observed increase in THOP1 expression might be part of a compensatory defense mechanism of the brain against an increased Aβ load.

Increased expression of the oligopeptidase THOP1 is a neuroprotective response to Aß toxicity / G.Pollio; JJ.Hoozemans; CA.Andersen ; R.Roncarati; MC.Rosi; ES.van Haastert ; T.Seredenina; D.Diamanti; S.Gotta; A. Fiorentini; L. Magnoni; R.Raggiaschi; AJ.Rozemuller; F.Casamenti; A.Caricasole; GC.Terstappen. - In: NEUROBIOLOGY OF DISEASE. - ISSN 0969-9961. - ELETTRONICO. - 31:(2008), pp. 145-158.

Increased expression of the oligopeptidase THOP1 is a neuroprotective response to Aß toxicity

CASAMENTI, FIORELLA;
2008

Abstract

In a comprehensive proteomics study aiming at the identification of proteins associated with amyloid-beta (Aβ)-mediated toxicity in cultured cortical neurons, we have identified Thimet oligopeptidase (THOP1). Functional modulation of THOP1 levels in primary cortical neurons demonstrated that its overexpression was neuroprotective against Aβ toxicity, while RNAi knockdown made neurons more vulnerable to amyloid peptide. In the TgCRND8 transgenic mouse model of amyloid plaque deposition, an age-dependent increase of THOP1 expression was found in brain tissue, where it co-localized with Aβ plaques. In accordance with these findings, THOP1 expression was significantly increased in human AD brain tissue as compared to nondemented controls. These results provide compelling evidence for a neuroprotective role of THOP1 against toxic effects of Aβ in the early stages of AD pathology, and suggest that the observed increase in THOP1 expression might be part of a compensatory defense mechanism of the brain against an increased Aβ load.
2008
31
145
158
G.Pollio; JJ.Hoozemans; CA.Andersen ; R.Roncarati; MC.Rosi; ES.van Haastert ; T.Seredenina; D.Diamanti; S.Gotta; A. Fiorentini; L. Magnoni; R.Raggiaschi; AJ.Rozemuller; F.Casamenti; A.Caricasole; GC.Terstappen
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Utilizza questo identificatore per citare o creare un link a questa risorsa: https://hdl.handle.net/2158/331321
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