Curcumin Modulates Platelet Activation and ROS Production Induced by Amyloid Peptides: New Perspectives in Attenuating Prothrombotic Risk in Alzheimer's Disease Patients.

BACKGROUND/

OBJECTIVES

Amyloid peptides, whose accumulation in the brain as senile plaques is associated with the onset of Alzheimer's disease, are also found in cerebral vessels and in circulation. In the bloodstream, amyloid peptides promote platelet adhesion, activation, oxidative stress, and thrombosis, contributing to the cardiovascular complications observed in Alzheimer's disease patients. Natural compounds, such as curcumin, are known to modulate platelet activation induced by the hemostatic stimuli thrombin and convulxin. In this study, we investigated the ability of curcumin to modulate platelet activation triggered by amyloid peptides, and we compared its effects with those displayed on platelet activation induced by physiological agonists.

METHODS

Commercial ultrapure curcumin was used, and platelet aggregation, granule secretion, phosphorylation of selected signaling proteins, and reactive oxygen species production were analyzed on isolated human platelets.

RESULTS

Our results demonstrate that curcumin effectively suppressed platelet aggregation induced by fibrillar amyloid peptides. This effect was associated with the reduction in intracellular signaling pathways involving PKC, PI3K, and MAPK. By contrast, platelet aggregation and activation induced by thrombin and convulxin were only partially reduced by preincubation with curcumin. Moreover, curcumin completely suppressed granule secretion only when platelets were stimulated with hemostatic agonists, but it had no effects upon stimulation with amyloid peptides. Additionally, curcumin reduced the production of reactive oxygen species induced by amyloid peptides with a stronger efficiency compared to platelets stimulated with thrombin.

CONCLUSIONS

These results indicate that curcumin displays selective and potent inhibitory activity on platelet responses to pathological stimuli, such as fibrillar amyloid peptides.