کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
3070670 | 1580739 | 2007 | 7 صفحه PDF | دانلود رایگان |
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 γ-secretase complex responsible for proteolytic processing of type I membrane proteins. p75NTR, a common neurotrophin receptor, was shown to be subject to γ-secretase processing. However, it is not clear if the p75NTR downstream signal is altered in response to γ-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 γ-secretase inhibition in SHSY-5Y cells. The activity of the small GTPase RhoA is strongly affected by these treatments. This study demonstrates that γ-secretase and PS2 play an important role in regulating neurotrophin signal transduction and either mutation of PS2 or inhibition of γ-secretase disturbs this function.
Journal: Neurobiology of Disease - Volume 27, Issue 3, September 2007, Pages 258–264