Statins are common drugs that are clinically used to reduce elevated plasma cholesterol levels. Based on their solubility, statins are considered to be either hydrophilic or lipophilic. Amongst them, simvastatin has the highest lipophilicity to facilitate its ability to cross the blood-brain barrier. Recent studies have suggested that simvastatin could be a promising therapeutic option for different brain complications and diseases ranging from brain tumors (i.e., medulloblastoma and glioblastoma) to neurological disorders (i.e., Alzheimer’s disease, Parkinson’s disease, and Huntington’s disease). Specific mechanisms of disease amelioration, however, are still unclear. Independent studies suggest that simvastatin may reduce the risk of developing certain neurodegenerative disorders. Meanwhile, other studies point towards inducing cell death in brain tumor cell lines. In this review, we outline the potential therapeutic effects of simvastatin on brain complications and review the clinically relevant molecular mechanisms in different cases.

The blood-brain barrier regulates the flow of ions, chemicals, and cells by acting as a conduit between blood and cerebral tissue. Additionally, it shields the brain against pathogen invasion and immune cell infiltration. It is composed of endothelial cells, pericytes, astrocytic end feet, perivascular macrophages, and microglial cells, which help in maintaining its integrity. There are various signaling pathways that are also involved in maintaining its integrity. The Wnt/β catenin, FZD4/FZD7, Hedgehog and TGF-β signaling pathways were evident to produce components or factors which stabilise the BBB. However, the NF-B and ERK signaling pathways caused the creation of MMPs, which increased the BBB's permeability. These functions are altered in pathological conditions like Alzheimer’s disease, and Parkinson’s disease which are also mentioned.