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Extra info for Alzheimer's Disease: Advances in Genetics, Molecular and Cellular Biology
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The S3 cleavage releases the Notch intracellular domain (NICD) that is subsequently translocated to the nucleus. NICD modulates target gene expression via binding to the CSL (CBF1/Suppressor of Hairless/Lag-1) family of transcription factors (Kopan and Goate 2000). While the genetics do not tell at what level PS inﬂuences the Notch signalling pathway, the mode of Notch processing is reminiscent of that of APP cleavage. , 1998), Notch1 processing was investigated in neurons and other cells derived from PS-deﬁcient mice (De Strooper et al.
However, APPs is necessary, but not sufﬁcient, for full activity, as it appears to act as a co-factor with EGF. If these ﬁndings are true in human brain, then the reduction in APPs levels in cerebrospinal ﬂuid of individuals with AD may indicate the loss of additional trophic activity in AD, together with the reduction of other growth factors in brain (see Chapter 15). 2 Cell adhesion An “RHDS” motif near the extralumenal portion of APP or at the Cterminus of APPs that is contained within the Aβ region appear to promote cell adhesion.
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