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CNS & Neurological Disorders - Drug Targets

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ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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Review Article

The β-Secretase Enzyme BACE1: A Biochemical Enigma for Alzheimer’s Disease

Author(s): Hirak Shah, Ashish Patel*, Vruti Parikh, Afzal Nagani, Bhargav Bhimani, Umang Shah and Tushar Bambharoliya

Volume 19, Issue 3, 2020

Page: [184 - 194] Pages: 11

DOI: 10.2174/1871527319666200526144141

Price: $65

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Abstract

Beta site amyloid precursor protein cleaving enzyme 1 (BACE1) is a rational target in Alzheimer’s Disease (AD) drug development due to its role in amyloidogenic cleavage of Amyloid Precursor Protein (APP) in generating Amyloid β (Aβ). This β-secretase cleaves not only Amyloid Precursor Protein (APP) and its homologues, but also small series of substrates including neuregulin and β subunit of voltage-gated sodium channel that play a very important role in the development and normal function of the brain. Moreover, BACE1 is modulated at the post-translational level by several factors that are associated with both physiological and pathological functions. Since the discovery of BACE1 over a decade ago, medicinal chemistry and pharmacokinetics of BACE1 small molecule inhibitors have proven challenging for the treatment of Alzheimer’s disease.

Keywords: Alzheimer's disease, Amyloid Precursor Protein (APP), BACE1, Amyloid β (Aβ), β-pathway, palmitoylation.

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