In vivo inhibition of Aβ production by memapsin 2 (β‐secretase) inhibitors
Open Access
- 7 May 2004
- journal article
- Published by Wiley in Journal of Neurochemistry
- Vol. 89 (6) , 1409-1416
- https://doi.org/10.1111/j.1471-4159.2004.02452.x
Abstract
We have previously reported structure-based design of memapsin 2 (β-secretase) inhibitors with high potency. Here we show that two such inhibitors covalently linked to a ‘carrier peptide’ penetrated the plasma membrane in cultured cells and inhibited the production of β-amyloid (Aβ). Intraperitoneal injection of the conjugated inhibitors in transgenic Alzheimer's mice (Tg2576) resulted in a significant decrease of Aβ level in the plasma and brain. These observations verified that memapsin 2 is a therapeutic target for Aβ reduction and also establish that transgenic mice are suitable in vivo models for the study of memapsin 2 inhibition.Keywords
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