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Notch‐1 activation by familial Alzheimer's disease (FAD)‐linked mutant forms of presenilin‐1
Author(s) -
Nakajima Mitsunari,
Shimizu Takahiko,
Shirasawa Takuji
Publication year - 2000
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/1097-4547(20001015)62:2<311::aid-jnr16>3.0.co;2-g
Subject(s) - presenilin , mutant , notch signaling pathway , biology , western blot , neuropathology , microbiology and biotechnology , intracellular , notch 1 , wild type , amyloid precursor protein , alzheimer's disease , chemistry , genetics , disease , medicine , pathology , signal transduction , gene
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 δE9 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 δE9 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. J. Neurosci. Res. 62:311–317, 2000. © 2000 Wiley‐Liss, Inc.