Molecular mechanisms underlying the effects of statins in the central nervous system

Int J Mol Sci. 2014 Nov 10;15(11):20607-37. doi: 10.3390/ijms151120607.

Abstract

3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, commonly referred to as statins, are widely used in the treatment of dyslipidaemia, in addition to providing primary and secondary prevention against cardiovascular disease and stroke. Statins' effects on the central nervous system (CNS), particularly on cognition and neurological disorders such as stroke and multiple sclerosis, have received increasing attention in recent years, both within the scientific community and in the media. Current understanding of statins' effects is limited by a lack of mechanism-based studies, as well as the assumption that all statins have the same pharmacological effect in the central nervous system. This review aims to provide an updated discussion on the molecular mechanisms contributing to statins' possible effects on cognitive function, neurodegenerative disease, and various neurological disorders such as stroke, epilepsy, depression and CNS cancers. Additionally, the pharmacokinetic differences between statins and how these may result in statin-specific neurological effects are also discussed.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism
  • Central Nervous System / pathology*
  • Central Nervous System Neoplasms / drug therapy
  • Central Nervous System Neoplasms / metabolism
  • Central Nervous System Neoplasms / pathology
  • Cognition / drug effects
  • Depression / drug therapy
  • Depression / metabolism
  • Depression / pathology
  • Epilepsy / drug therapy
  • Epilepsy / metabolism
  • Epilepsy / pathology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Neurodegenerative Diseases / drug therapy
  • Neurodegenerative Diseases / metabolism
  • Neurodegenerative Diseases / pathology
  • Stroke / drug therapy
  • Stroke / metabolism
  • Stroke / pathology

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors