Abstract
Alzheimer's disease (AD) is one of the most common neurodegenerative diseases without any effective medicine treatments. The neurofibrillary tangles containing hyperphosphorylated tau protein are one important pathological characteristic. Thus, one practicable strategy for AD drug design is to discover compounds that could inhibit tau protein aggregation and/or phosphorylation. In this study, isobavachalcone, a natural plant-derived compound, has been shown to inhibit tau protein aggregation and disaggregate tau fibrils in vitro by directly interacting with tau protein at amino acids I278, V309, etc. It is able to reduce tau phosphorylation at four disease-related sites in vivo by regulating the critical kinase and protein phosphatase, GSK3β and PP2A. The compound also exhibits protection against tau oligomers-induced apoptosis through the mitochondria and ER mediated apoptotic pathways. In summary, isobavachalcone is a promising candidate for further evaluation as a potential preventive and therapeutic medicine for AD.