Resveratrol is a naturally occurring compound contributing to cellular defense mechanisms in plants. Its use as a nutritional component and/or supplement in a number of diseases, disorders, and syndromes such as chronic diseases of the central nervous system, cancer, inflammatory diseases, diabetes, and cardiovascular diseases has prompted great interest in the underlying molecular mechanisms of action. The present review focuses on resveratrol, specifically its isomer trans-resveratrol, and its effects on intracellular calcium signaling mechanisms. As resveratrol's mechanisms of action are likely pleiotropic, its effects and interactions with key signaling proteins controlling cellular calcium homeostasis are reviewed and discussed. The clinical relevance of resveratrol's actions on excitable cells, transformed or cancer cells, immune cells and retinal pigment epithelial cells are contrasted with a review of the molecular mechanisms affecting calcium signaling proteins on the plasma membrane, cytoplasm, endoplasmic reticulum, and mitochondria. The present review emphasizes the correlation between molecular mechanisms of action that have recently been identified for resveratrol and their clinical implications.

SUMMARY Presenilins (PS), endoplasmic reticulum (ER) transmembrane proteins, form the catalytic core of γ-secretase, an amyloid precursor protein processing enzyme. Mutations in PS lead to Alzheimer's disease (AD) by altering γ-secretase activity to generate pathologic amyloid beta and amyloid plaques in the brain. Here, we identified a novel mechanism where binding of the soluble, cytosolic N-terminal domain (NTF) of PS to intracellular Ca2+ release channels, ryanodine receptors (RyR), controls Ca2+ release from the ER. While PS1NTF decreased total RyR-mediated Ca2+ release, PS2NTF had no effect at physiological Ca2+ concentrations. This differential function and isotype-specificity is due to four cysteines absent in PS1NTF, present, however, in PS2NTF. Site-directed mutagenesis targeting these cysteines converted PS1NTF to PS2NTF function and vice versa, indicating differential RyR binding. This novel mechanism of intracellular Ca2+ regulation through the PS-RyR interaction represents a novel target for AD drug development and the treatment of other neurodegenerative disorders that critically depend on ryanodine receptor and presenilin signaling.

Circulating Gal-3 levels showed a statistically significant decrease in humans undergoing therapeutic LA. Although absolute Gal-3 reduction was ≈19-23%, this effect, combined with reducing atherogenic LDL and other inflammation mediators (e.g., CRP, fibrinogen, Lp-PLA2 ), may enhance apheresis clinical benefits. Applying new Gal-3-specific extraction technologies to apheresis may be advantageous in treating diverse pathologies that are promoted by elevated plasma Gal-3. J. Clin. Apheresis 31:388-392, 2016. © 2015 Wiley Periodicals, Inc.

No abstract