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The BACE inhibitor NB-360 in preclinical models: From β-amyloid reduction to downstream disease-relevant effects

Neumann, Ulf and Machauer, Rainer and Shimshek, Derya (2019) The BACE inhibitor NB-360 in preclinical models: From β-amyloid reduction to downstream disease-relevant effects. British journal of pharmacology, 176. pp. 1-12.

Abstract

Inhibition of Beta-site- APP Cleaving Enzyme-1 (BACE-1) is a current approach to fight the β-amyloid (Aβ) deposition in the brains of patients with Alzheimer’s disease, and a number of BACE-1 inhibitors are currently being tested in clinical trials. The BACE-1 inhibitor NB-360, although not a clinical compound, turned out as a valuable pharmacological tool to investigate the effects of BACE-1 inhibition on the deposition of different Aβ species in APP transgenic mice. Furthermore, chronic animal studies with NB-360 discovered relationships between BACE-1 inhibition, Aβ deposition, and Aβ-related downstream effects on neuroinflammation, neuronal function and markers of neurodegeneration. NB-360 effects on the processing of physiological BACE-1 substrates as well as on non-enzymatic BACE-1 functions have been investigated and complement studies performed with BACE-1 knock-out mice. Since NB-360 is also an inhibitor for BACE-2, non-clinical studies revealed physiological effects of BACE-2 inhibition.

Item Type: Article
Date Deposited: 28 May 2019 00:45
Last Modified: 28 May 2019 00:45
URI: https://oak.novartis.com/id/eprint/36938

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