NDLI: β-Secretase as a therapeutic target for Alzheimer’s disease

Content Provider	Springer Nature Link
Author	Ghosh, Arun K. Gemma, Sandra Tang, Jordan
Copyright Year	2008
Abstract	β-Secretase (memapsin 2, BACE1) is an attractive target for the development of inhibitor drugs to treat Alzheimer’s disease (AD). Not only does this protease function at the first step in the pathway leading to the production of amyloid-β (Aβ), its gene deletion produces only mild phenotypes. In addition, β-secretase is an aspartic protease whose mechanism and inhibition are well known. The development of β-secretase inhibitors, actively pursued over the last seven years, has been slow, due to the difficulty in combining the required properties in a single inhibitor molecule. Steady progress in this field, however, has brought about inhibitors that contain many targeted characteristics. In this review, we describe the strategy of structure-based inhibitor evolution in the development of β-secretase inhibitor drug. The current status of the field offers grounds for some optimism, in that β-secretase inhibitors have been shown to reduce brain Aβ and to rescue the cognitive decline in transgenic AD mice, and an orally available β-secretase inhibitor drug candidate is in clinical trial. With this knowledge base, it seems reasonable to expect that more drug candidates will be tested in human, and then successful disease-modifying drugs may ultimately emerge from this target.
Starting Page	399
Ending Page	408
Page Count	10
File Format	PDF
ISSN	19337213
Journal	NeuroRX
Volume Number	5
Issue Number	3
e-ISSN	18787479
Language	English
Publisher	Springer-Verlag
Publisher Date	2008-01-01
Publisher Institution	American Society for Experimental NeuroTherapeutics
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	β-secretase amyloid precursor protein secretase inhibitor drug Alzheimer’s disease Neurosciences Neurology Neurosurgery Neurobiology
Content Type	Text
Resource Type	Article
Subject	Neurology (clinical) Pharmacology Pharmacology (medical)

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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