In Greek and Roman times, theriaca, a first century AD concoction, was considered as a panacea, a remedy good for all kind of illnesses. Statins are a sort of twenty-first century theriaca. Indeed drugs in this class represent not only the best treatment for hypercholesterolemia – at least in theory – but also a remedy potentially useful in a growing list of conditions including osteoporosis, Alzheimer’s disease, depression, hypertension, sepsis, and cancer [1]. Such a wide therapeutic potential depends on the fact that statins impinge upon a series of signaling molecules (see below) which are fundamental for physiological cell functioning. Interference with these molecular mechanisms results in a variety of effects at organ or system level, like immune system and central nervous system (CNS) modulation, bone marrow progenitor cells mobilization and regulation of bone physiology and repair. Furthermore, beyond cholesterol lowering, vasculo-protection by statins depends also on other key mechanisms implicated in the atherosclerosis process, including endothelial dysfunction, atherosclerotic plaques stabilization, oxidative stress and inflammation, and the thrombogenic response to vascular injury [2]. Most of these pleiotropic effects are mediated by inhibition of isoprenoids, a fundamental series of compounds that serve as lipid attachments for intracellular signaling molecules. In particular, inhibition of small GTP-binding proteins – including Rac, Rho, and Ras – whose proper membrane localization and function are dependent on isoprenylation, is considered as a central mechanism in mediating the pleiotropic effects of statins [3].
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