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.
Coimbra JRM, Marques DFF, Baptista SJ, et al. Highlights in BACE1 Inhibitors for Alzheimer’s Disease Treatment. Front Chem 2018; 6: 178.
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