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


Autoria(s): Ito, Yoshio; Ishii, Azusa; Passmore, A Peter; McIlroy, Stephen P
Data(s)

01/09/2007

Resumo

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.

Identificador

http://pure.qub.ac.uk/portal/en/publications/analysis-of-alteration-of-p75ntr-processing-and-signalling-by-ps2-mutation-and-gammasecretase-inhibition(8cd3b8a8-af3c-41fb-b9a7-70eb578b22e5).html

http://dx.doi.org/10.1016/j.nbd.2007.05.002

Idioma(s)

eng

Direitos

info:eu-repo/semantics/restrictedAccess

Fonte

Ito , Y , Ishii , A , Passmore , A P & McIlroy , S P 2007 , ' Analysis of alteration of p75NTR processing and signalling by PS2 mutation and gamma-secretase inhibition ' Neurobiology of disease , vol 27 , no. 3 , pp. 258-64 . DOI: 10.1016/j.nbd.2007.05.002

Palavras-Chave #/dk/atira/pure/subjectarea/asjc/2800/2808 #Neurology
Tipo

article