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Is BACE1 a suitable therapeutic target for the treatment of Alzheimer's disease? Current strategies and future directions
Citation
Klaver, DW and Wilce, MCJ and Cui, H and Hung, AC and Gasperini, R and Foa, L and Small, DH, Is BACE1 a suitable therapeutic target for the treatment of Alzheimer's disease? Current strategies and future directions, Biological Chemistry: Official Journal of The German Society for Biochemistry and Molecular Biology, 391, (8) pp. 849-859. ISSN 1431-6730 (2010) [Refereed Article]
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Copyright Statement
Copyright © 2010 Walter de Gruyter.
Abstract
Alzheimer’s disease (AD) is characterized by the extracellular
deposition of the b-amyloid protein (Ab). Ab is a fragment
of a much larger precursor protein, the amyloid
precursor protein (APP). Sequential proteolytic cleavage of
APP by b-secretase and g-secretase liberates Ab from APP.
The aspartyl protease BACE1 (b-site APP-cleaving enzyme
1) catalyses the rate-limiting step in the production of Ab,
and as such it is considered to be a major target for drug
development in Alzheimer’s disease. However, the development
of a BACE1 inhibitor therapy is problematic for two
reasons. First, BACE1 has been found to have important
physiological roles. Therefore, inhibition of the enzyme
could have toxic consequences. Second, the active site of
BACE1 is relatively large, and many of the bulky compounds
that are needed to inhibit BACE1 activity are unlikely
to cross the blood-brain barrier. This review focuses on
the structure BACE1, current therapeutic strategies based on
developing active-site inhibitors, and new approaches to
therapy involving targeting the expression or post-translational
regulation of BACE1.
Item Details
| Item Type: | Refereed Article |
|---|---|
| Keywords: | Alzheimer’s disease, amyloid, beta-secretase, beta-site APP cleaving enzyme (BACE), protease, therapy |
| Research Division: | Medical and Health Sciences |
| Research Group: | Neurosciences |
| Research Field: | Neurosciences not elsewhere classified |
| Objective Division: | Health |
| Objective Group: | Clinical Health (Organs, Diseases and Abnormal Conditions) |
| Objective Field: | Neurodegenerative Disorders Related to Ageing |
| Author: | Klaver, DW (Mr David Klaver) |
| Author: | Cui, H (Mr Hao Cui) |
| Author: | Hung, AC (Dr Amos Hung) |
| Author: | Gasperini, R (Dr Rob Gasperini) |
| Author: | Foa, L (Professor Lisa Foa) |
| Author: | Small, DH (Professor David Small) |
| ID Code: | 65156 |
| Year Published: | 2010 |
| Web of Science® Times Cited: | 28 |
| Deposited By: | Menzies Institute for Medical Research |
| Deposited On: | 2010-10-07 |
| Last Modified: | 2013-02-18 |
| Downloads: | 7 View Download Statistics |
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