Analysis of alteration of p75NTR processing and signalling by PS2 mutation and gamma-secretase inhibition

Yoshio Ito, Azusa Ishii, A Peter Passmore, Stephen P McIlroy

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

The presenilins (PSs) were identified as causative genes in cases of early-onset familial Alzheimer's disease (AD) and current evidence indicates that PSs are part of the gamma-secretase complex responsible for proteolytic processing of type I membrane proteins. p75NTR, a common neurotrophin receptor, was shown to be subject to gamma-secretase processing. However, it is not clear if the p75NTR downstream signal is altered in response to gamma-secretase cleavage, and further there is a possibility that AD-related PS mutations may affect this cleavage, resulting in pathogenic alterations in signal transduction. In this study, we confirmed that p75NTR downstream signalling is altered by PS2 mutation or gamma-secretase inhibition in SHSY-5Y cells. The activity of the small GTPase RhoA is strongly affected by these treatments. This study demonstrates that gamma-secretase and PS2 play an important role in regulating neurotrophin signal transduction and either mutation of PS2 or inhibition of gamma-secretase disturbs this function.
Original languageEnglish
Pages (from-to)258-64
Number of pages7
JournalNeurobiology of disease
Volume27
Issue number3
DOIs
Publication statusPublished - Sep 2007

ASJC Scopus subject areas

  • Neurology

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