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

Abstract：

:In a comprehensive proteomics study aiming at the identification of proteins associated with amyloid-beta (Abeta)-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 Abeta 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 Abeta 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 Abeta 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 Abeta load.

journal_name

Neurobiol Dis

journal_title

Neurobiology of disease

authors

Pollio G,Hoozemans JJ,Andersen CA,Roncarati R,Rosi MC,van Haastert ES,Seredenina T,Diamanti D,Gotta S,Fiorentini A,Magnoni L,Raggiaschi R,Rozemuller AJ,Casamenti F,Caricasole A,Terstappen GC

doi

10.1016/j.nbd.2008.04.004

subject

Has Abstract

pub_date

2008-07-01 00:00:00

pages

145-58

issue

1

eissn

0969-9961

issn

1095-953X

pii

S0969-9961(08)00074-0

journal_volume

31

pub_type

杂志文章

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