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, Tushar Bambharoliya

Journal Name: CNS & Neurological Disorders - Drug Targets
Formerly Current Drug Targets - CNS & Neurological Disorders

Volume 19 , Issue 3 , 2020


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Graphical Abstract:


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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VOLUME: 19
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