Pleiotropic use of Statins as non-lipid-lowering drugs

Abstract

Statins, known as HMG-CoA reductase (HMGCR) inhibitors, have primarily been utilized for metabolic and angiographic medical applications because of their cholesterol-lowering effects. Similar to other drugs, statins may also induce a series of potential side effects. Statins inhibit the HMGCR (rate-limiting enzyme) activity in early stages of mevalonate pathway and then indirectly affect a number of intermediate products, including non-sterol isoprenoids (coenzyme Q10, dolichol etc.), which can result in impaired functions of body organs. Recently, scores of studies have uncovered additional functional mechanisms of statins in other diseases, such as diabetes mellitus, nervous system diseases, coronary heart disease, inflammation and cancers. This review aims to summarize the positive and adverse mechanisms of statin therapy. Statin care should be taken in the treatment of many diseases including cancers. Since the underlying mechanisms are not fully elucidated, future studies should spend more time and efforts on basic research to explore the mechanisms of statins.

Simvastatin accelerated motoneurons death in SOD1G93A mice through inhibiting Rab7-mediated maturation of late autophagic vacuoles

“…The inhibitory function of statins on HMG-CoA reductase resulted in depletion of cholesterol and isoprenoids in MVA pathway 19 , 55 . Statins thus have therapeutic application in diseases like inflammatory disease, cancer, and neurodegenerative disease including AD, PD, and MS, probably due to its pleiotropic effects independent of lowering cholesterol levels 24 – 26 , 56 . However, impacts of statins on ALS have gained less attention.…”

“…By lowing LDL levels, statins have been widely used in the clinic for treating hypercholesterolemia, cardiovascular, and cerebrovascular disease 21 – 23 . Moreover, the pleiotropic effects (independent cholesterol) of statins have a protective effect in many diseases, including AD, PD, and multiple sclerosis (MS) 24 – 26 . However, accumulating data have suggested that statins increased risk of diabetes, liver disorders, or myopathy 27 – 29 .…”

Statins: a repurposed drug to fight cancer

“…The effect of statins on cardiovascular morbidity and mortality in patients with and without atherosclerotic disease has been well proven. Furthermore, statins appear to exert pleiotropic effects independent of their lipid-lowering properties, including effects on diabetes, neurological diseases, coronary heart disease, inflammation and cancer [ 16 ]. Given the anticancer effects of statins, and the fact that statins are well-tolerated, inexpensive, and less toxic than conventional chemotherapy drugs, many researchers considered repurposing statins as a promising strategy for the treatment of cancer.…”

Rosuvastatin Nanomicelles Target Neuroinflammation and Improve Neurological Deficit in a Mouse Model of Intracerebral Hemorrhage

“…They are not only used to reduce low-density lipoprotein (LDL) cholesterol and prevent cardiovascular diseases but also play a role in many other conditions, including inhibiting inflammatory reaction, antioxidants, improving endothelial function, and even inhibiting mitosis of cancer cells. [5][6][7][8] For example, statin was identified as a potential neuroprotective agent that targeted the inflammatory response following ICH. However, the use of statin was usually limited by its inherent drawbacks.…”