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

Sarco/endoplasmic reticulum Ca-ATPase (SERCA) is a key protein responsible for transporting Ca ions from the cytosol into the lumen of the sarco/endoplasmic reticulum (SR/ER), thus maintaining Ca homeostasis within cells. Accumulating evidence suggests that impaired SERCA function is associated with disruption of intracellular Ca homeostasis and induction of ER stress, leading to different chronic pathological conditions. Therefore, appropriate strategies to control Ca 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 signaling pathways. In this review, potential Ca-mediated effects of the most studied polyphenols on SERCA pumps or related Ca signaling pathways are summarized, and relevant mechanisms of their action on Ca 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).