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P4–330: Substrate concentration dependent inhibition of gamma secretase by novel inhibitors
Author(s) -
Hemphill Susanna S.,
Ren Zhao,
Neitzel Martin L.,
Marugg Jennifer L.,
Jagodzinski Jacek,
Latimer Lee H.,
Pleiss Michael A.,
Freedman Stephen B.,
Sinha Sukanto,
Shapiro I. Paul,
Basi Guriqbal S.
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.2071
Subject(s) - proteases , potency , chemistry , enzyme , amyloid precursor protein secretase , gamma secretase , biochemistry , peptide , in vivo , inhibitory postsynaptic potential , amyloid precursor protein , in vitro , pharmacology , microbiology and biotechnology , alzheimer's disease , biology , neuroscience , medicine , disease
A 42-induced neurotoxicity and reduce A deposits in the brain of 3xTg-AD mice. Polyclonal as well as 6E10 monoclonal antibodies inhibit neurotoxicity induced by A fibrils, but only the former is relatively potent in reducing toxicity induced by A oligomers. Both antibodies significantly reduce the A plaque burden in 3xTg-AD mice after a single intrahippocampal injection. Conclusions: Thus, anti-A 1-11 antibodies are effective against all pathological forms of the A peptide, including most toxic oligomers, which suggests the potential utility of our novel AD vaccine.