Journal
BIOLOGICAL CHEMISTRY
Volume 388, Issue 9, Pages 979-983Publisher
WALTER DE GRUYTER GMBH
DOI: 10.1515/BC.2007.117
Keywords
a beta; Ac-LVK-CHO; Alzheimer's disease; beta-amyloid; beta-secretase; cathepsin B; cysteine protease; inhibitor
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Funding
- NIA NIH HHS [AG 18044] Funding Source: Medline
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beta-Secretase inhibitors that lower brain beta-amyloid peptides (A beta) are likely to be effective for treating Alzheimer's disease (AD). Irreversible epoxysuccinyl cysteine protease inhibitors are known to reduce brain A beta and beta-secretase activity in the guinea pig model of human A beta production. In this study, acetyl-L-leucyl-L-valyl-L-lysinal (Ac-LVK-CHO) is also shown to significantly reduce brain A beta and beta-secretase activity and brain A beta in the same model. Ac-LVK-CHO 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.
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