Natural compounds that modulate BACE1-processing of amyloid-beta precursor protein in Alzheimer's disease

Alzheimer's disease (AD) is a fatal neurodegenerative disorder and the primary cause of dementia, with no cure presently available. The pathogenesis of AD is believed to be primarily driven by amyloid-β (Aβ), the principal component of senile plaques in the AD brain. Aβ is generated through a sequential proteolytic process initiated by BACE1, or β-secretase, from the amyloid-β precursor protein (APP). BACE1-cleavage of APP is the rate-limiting step in producing Aβ; therefore, much of the effort has focused on identifying BACE1 inhibitors. More recently, an AD clinical trial using a BACE1 inhibitor was halted due to adverse effects outside of the brain in animal models. This raised questions with respect to the physiological roles of BACE1 and the approach in identifying lead compounds to inhibit BACE1 with desirable safety profiles. Natural products, particularly those utilized in traditional Chinese medicine (TCM), have an advantage in their safety profiles because they have already been utilized in humans for a long time. This article will discuss the background of AD and the biological aspects of BACE1, and then discuss the effects of several natural products that modulate BACE1-processing of APP.