Natural Polyphenols as SERCA Activators: Role in the Endoplasmic Reticulum Stress-Related Diseases

Sarco/endoplasmic reticulum Ca(2+)-ATPase (SERCA) is a key protein responsible for transporting Ca(2+) ions from the cytosol into the lumen of the sarco/endoplasmic reticulum (SR/ER), thus maintaining Ca(2+) homeostasis within cells. Accumulating evidence suggests that impaired SERCA function is associated with disruption of intracellular Ca(2+) homeostasis and induction of ER stress, leading to different chronic pathological conditions. Therefore, appropriate strategies to control Ca(2+) homeostasis via modulation of either SERCA pump activity/expression or relevant signaling pathways may represent a useful approach to combat pathological states associated with ER stress. Natural dietary polyphenolic compounds, such as resveratrol, gingerol, ellagic acid, luteolin, or green tea polyphenols, with a number of health-promoting properties, have been described either to increase SERCA activity/expression directly or to affect Ca(2+) signaling pathways. In this review, potential Ca(2+)-mediated effects of the most studied polyphenols on SERCA pumps or related Ca(2+) signaling pathways are summarized, and relevant mechanisms of their action on Ca(2+) regulation with respect to various ER stress-related states are depicted. All data were collected using scientific search tools (i.e., Science Direct, PubMed, Scopus, and Google Scholar).