Natural Products Targeting Amyloid Beta in Alzheimer's Disease

Abstract

Alzheimer's disease (AD) is a neurodegenerative disease characterized by severe brain damage and dementia. There are currently few therapeutics to treat this disease, and they can only temporarily alleviate some of the symptoms. The pathogenesis of AD is mainly preceded by accumulation of abnormal amyloid beta (A beta) aggregates, which are toxic to neurons. Therefore, modulation of the formation of these abnormal aggregates is strongly suggested as the most effective approach to treat AD. In particular, numerous studies on natural products associated with AD, aiming to downregulate A beta peptides and suppress the formation of abnormal A beta aggregates, thus reducing neural cell death, are being conducted. Generation of A beta peptides can be prevented by targeting the secretases involved in A beta-peptide formation (secretase-dependent). Additionally, blocking the intra- and intermolecular interactions of A beta peptides can induce conformational changes in abnormal A beta aggregates, whereby the toxicity can be ameliorated (structure-dependent). In this review, AD-associated natural products which can reduce the accumulation of A beta peptides via secretase- or structure-dependent pathways, and the current clinical trial states of these products are discussed.