Nakajima M, Shimizu T, Shirasawa T
Department of Molecular Genetics, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
J Neurosci Res. 2000 Oct 15;62(2):311-7. doi: 10.1002/1097-4547(20001015)62:2<311::AID-JNR16>3.0.CO;2-G.
We prepared a cleavage site-directed antibody against Notch-1, that specifically recognized the cleaved Notch-1 intracellular domain (NICD). To assess Notch-1 processing and its nuclear localization in familial Alzheimer's disease (FAD)-linked presenilin-1 (PS-1) mutants, we overexpressed wild type, M146V, A246E, C410Y, or deltaE9 PS-1 mutant with a membrane-bound Notch-1 in a PS-1-deficient cell line. On Western blot and immunocytochemical analyses using the NICD specific antibody, M146V and A246E mutants showed the comparable levels of Notch-1 processing and nuclear localizing activities to wild type PS-1 whereas C410Y and deltaE9 mutants failed to show these activities. These results suggest that the loss or partial loss of PS-1 activities in Notch-1 proteolysis and its nuclear translocation may be irrelevant for the neuropathology of Alzheimer's disease.
