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Understanding BACE1: essential protease for amyloid-β production in Alzheimer’s disease

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Abstract.

The identification of the aspartic protease BACE1 (β-secretase) was a defining event in research aimed at understanding the molecular mechanisms that underlie Alzheimer’s disease (AD) pathogenesis. This is because BACE1 catalyses the rate limiting step in the production of amyloid-β (Aβ) the principal component of plaque pathology in AD, the excessive production of which is believed to be a primary cause of neurodegeneration, and cognitive dysfunction in AD. Subsequent discoveries showed that genetic deletion of BACE1 completely abolishes Aβ production and deposition in vivo, and that BACE1 activity is significantly increased in AD brain. In this review we present current knowledge on BACE1, discussing its structure, function and complex regulation with a view to understanding BACE1 function in the brain, and BACE1 as a target in blocking aberrant Aβ production in AD.

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Correspondence to C. O’Neill.

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Received 15 May 2008; received after revision 13 June 2008; accepted 18 June 2008

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Stockley, J.H., O’Neill, C. Understanding BACE1: essential protease for amyloid-β production in Alzheimer’s disease. Cell. Mol. Life Sci. 65, 3265–3289 (2008). https://doi.org/10.1007/s00018-008-8271-3

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  • DOI: https://doi.org/10.1007/s00018-008-8271-3

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