University of California
Dr. Nazneen Dewji is an Associate Professor at the University of California, San Diego. Nazneen was born in Tanzania and raised in England. She earned her B.Sc. (Hons.) in Biochemistry in 1978 and her Ph.D. in 1982 at the University of London. In 1986 Nazneen joined the department of Medicine at UCSD, where she began working on Alzheimer's disease (AD). The discoveries made in her laboratory support the development of new drug discovery targets for the treatment of AD. In 2006 Nazneen founded a company, Cenna Biosciences Inc., to further develop novel candidates for the treatment of AD.
A� accumulation is critical to the development of Alzheimer�s disease (AD). Current efforts at reducing A� 40 or 42 have focused on modulating ?-secretase to produce shorter A�, while attempting to spare other secretase functions. Earlier attempts at lowering total A� were unsatisfactory as they targeted the catalytic activities of �- or ?-secretase, enzymes known to also hydrolyze other substrates. New therapeutic approaches that can inhibit total A� without altering secretase activity are therefore of great interest. Here we demonstrate such a new, different and early approach for the treatment of AD. We previous showed that an interaction between APP and Presenilin (PS) in cell cultures is a required initial step in the ultimate production of A� from APP. Furthermore, if the entire NH2-terminal domain of the PS was first added to the culture, the amount of A� produced was significantly reduced. We exploited the potential therapeutic significance of these results: to inquire whether isolated small soluble peptides within the NH2-terminal domain of PS-1 retained enough of the inhibitory activity of the whole domain, such that when added to model systems of AD, they effectively reduced A� production. Here we demonstrate that two small, non-over-lapping water-soluble peptides, P4 and P8 can substantially and specifically inhibit A� production in vitro and in the brains of APP transgenic mice. These peptide-induced reductions of total A� (and of A�40 and 42) did not alter �- or ?-secretase activities. P4 and P8 offer new and effective potential drug candidates for the treatment of AD.