Protocatechuic Acid: Inhibition of Fibril Formation, Destabilization of Preformed Fibrils of Amyloid-β and α-Synuclein, and Neuroprotection

Protocatechuic acid (PCA) is the major metabolite of the anthocyanin known as cyanidin 3-glucoside. It is found in plasma and tissues, such as the brain, heart, liver, and kidneys, following consumption of a rich source of this flavonoid. The abnormal pathological assembly of amyloid-beta (A beta) and alpha-synuclein (alpha S) is an underlying mechanism involved in the formation of amyloid plaques and Lewy bodies in the brain, which are responsible for neuropathology symptoms in Alzheimer's (AD) and Parkinson's diseases (PD), respectively. This research was performed to evaluate the protective effects of PCA, by establishing its potential role in inhibiting aggregation and fibril destabilization of A beta and alpha S proteins. It has been found that PCA inhibits the aggregation of A beta and alpha S and destabilizes their preformed fibrils. These results were confirmed by TEM images, electrophoresis, and immunoblotting experiments. Furthermore, PCA prevents the death of PC12 cells triggered by A beta- and alpha S-induced toxicity.