Alzheimer’s disease (AD) is characterized by impaired cognitive functions
due to irreversible neuronal injury by the formation of abnormal beta-amyloid plaques
(aggregated amyloid beta-peptide (AβP)) in the brain. Among various secretase
enzymes, beta-site amyloid precursor protein-cleaving enzyme-1 (BACE1) functions in
the first step and is the rate-limiting step of the AβP formation. Therefore, BACE1 has
attained considerable attention as a novel therapeutic target for the management of AD.
Inhibition of BACE1 prevents the generation of amyloid-beta and hence blocks the
impending pathological events that occur due to beta peptide accumulation. The drugs
being used clinically (acetylcholinesterase inhibitors and NMDA receptor antagonists)
so far have not been able to cure AD completely and are associated with a high risk of
toxicity. Thus, finding a newer therapeutic regimen for AD is of utmost importance and
BACE1 could be a potential target for developing newer drugs.
Plants are described as memory enhancers in various ancient systems of medicines,
including Ayurveda and Traditional Chinese System, and thus, are being used by
mankind for improving intellect skills and cognition. Recently, research has paid much
attention to the drugs of natural origin as these are generally considered safe and
devoid of side effects. Therefore, herbal extracts are explored for specific BACE1
inhibitory activity, and compounds (BACE1 inhibitors) are isolated. There are several
plant extracts and phytoconstituents that have demonstrated marked BACE1 inhibitor
activity along with superior biosafety. This chapter highlights the role of BACE1 in the
pathogenesis of memory deficit associated with AD and draws attention to the distinct
potential natural BACE1 inhibitors for AD treatment.
Keywords: Alzheimer’s disease, Amyloid-beta, BACE 1, Clinical trials, Cognitive impairment, Flavonoids, Natural products, Neurodegeneration, Noveltarget, Phenols.
