Molecular mechanisms underlying the effects of statins in the central nervous system.
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.
School of Pharmacy, Griffith University, Queensland 4222, Australia. a.mcfarland@griffith.edu.au.
Amelia J
AJ
McFarland
School of Pharmacy, Griffith University, Queensland 4222, Australia. s.dukie@griffith.edu.au.
Shailendra
S
Anoopkumar-Dukie
School of Pharmacy, Griffith University, Queensland 4222, Australia. d.arora@griffith.edu.au.
Devinder S
DS
Arora
School of Pharmacy, Griffith University, Queensland 4222, Australia. g.grant@griffith.edu.au.
Gary D
GD
Grant
Department of Biomedical Science, Bond University, Queensland 4226, Australia. camcderm@bond.edu.au.
Catherine M
CM
McDermott
Griffith Health Institute, Griffith University, Queensland 4222, Australia. a.perkins@griffith.edu.au.
Anthony V
AV
Perkins
School of Pharmacy, Griffith University, Queensland 4222, Australia. a.davey@griffith.edu.au.
Andrew K
AK
Davey
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D016543:Central Nervous System Neoplasms / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D003071:Cognition / Q000187:drug effects; D003863:Depression / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004827:Epilepsy / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000627:therapeutic use; D019636:Neurodegenerative Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors