학술논문
Increased expression of the oligopeptidase THOP1 is a neuroprotective response to Aβ toxicity
Document Type
article
Author
Giuseppe Pollio; Jeroen J.M. Hoozemans; Claus A. Andersen; Renza Roncarati; Maria Cristina Rosi; Elise S. van Haastert; Tamara Seredenina; Daniela Diamanti; Stefano Gotta; Anna Fiorentini; Letizia Magnoni; Roberto Raggiaschi; Annemieke J.M. Rozemuller; Fiorella Casamenti; Andrea Caricasole; Georg C. Terstappen
Source
Neurobiology of Disease, Vol 31, Iss 1, Pp 145-158 (2008)
Subject
Language
English
ISSN
1095-953X
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 non-demented 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.