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Gregory Hook, Vivian Y.H. Hook, Mark Kindy

Cysteine protease inhibitors reduce brain ?-amyloid and ?-secretase activity in vivo and are potential Alzheimer's disease therapeutics

Keywords: A?, ?-amyloid, ?-secretase, cysteine protease, cathepsin B, inhibitor, Ac-LVK-CHO

?-Secretase inhibitors that lower brain ?-amyloid peptides (A?) are likely to be effective for treating Alzheimer's disease (AD). Irreversible epoxysuccinyl cysteine protease inhibitors are known to reduce brain A? and ?-secretase activity in the guinea pig model of human A? production. In this study, acetyl-L-leucyl-L-valyl-L-lysinal (Ac-LVK-CHO) is also shown to significantly reduce brain Aß and ?-secretase activity and brain Aß in that model. Ac-LVKCHO is structurally distinct from the epoxysuccinyl inhibitors and is a reversible cysteine protease inhibitor. The results suggest that cysteine protease inhibitors generally, and reversible cysteine protease inhibitors specifically, have potential for development as AD therapeutics.

Biological Chemistry, Walter de Gruyter

Print ISSN: 1431-6730
Volume: 2007
Pages: -

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