Study of memapsin 2 (β-secretase) and strategy of inhibitor design

Authors: Tang, Jordan¹; Ghosh, Arun²; Hong, Lin³; Koelsch, Gerald³; Turner, Robert⁴; Chang, Wanpin⁴

Source: Journal of Molecular Neuroscience, Volume 20, Number 3, August 2003 , pp. 299-304(6)

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Abstract:

The discovery that β-secretase is a membrane-anchored aspartic protease memapsin 2 has stimulated much interest in the design and testing of its inhibitors for the treatment of Alzheimer's disease. This article discusses the strategy for the development of such inhibitor drugs. Enzymology and structural determination tools have permitted the design of memapsin 2 inhibitors with high potency and in a size range possible for penetration of the blood-brain barrier. Transgenic Alzheimer's mice have been used to show that when memapsin 2 inhibitors are transported to the brain, they effectively reduce the production of amyloid β. Although development of a clinical candidate of memapsin 2 inhibitor drug remains a very challenging undertaking, the progress so far lends some optimism for future prospects.

Keywords: Alzheimer's disease; β-secretase; memapsin 2; aspartic protease; inhibitor drugs

Document Type: Research article

DOI: http://dx.doi.org/10.1385/JMN:20:3:299

Affiliations: 1: Protein Studies Program, Oklahoma Medical Research Foundation, 73104, Oklahoma City, OK, Email: jordan-tang@omrf.ouhsc.edu 2: Department of Chemistry, University of Illinois at Chicago, Chicago, IL, 3: Zapaq, Inc., Oklahoma City, OK, 4: Protein Studies Program, Oklahoma Medical Research Foundation, 73104, Oklahoma City, OK,

Publication date: 2003-08-01