Statins and the Brain: More than Lipid Lowering Agents?
Author:
Fracassi Anna1, Marangoni Martina2, Rosso Pamela1, Pallottini Valentina1, Fioramonti Marco3, Siteni Silvia1, Segatto Marco4
Affiliation:
1. Department of Science, University of Rome , Italy 2. Medical Genetics Unit, University Hospital of Rome , Italy 3. Universite Libre de Bruxelles (ULB), IRIBHM, Bruxelles, Belgium 4. Department of Sense Organs, Sapienza University of Rome, Italy
Abstract
Background:
Statins represent a class of medications widely prescribed to efficiently
treat dyslipidemia. These drugs inhibit 3-βhydroxy 3β-methylglutaryl Coenzyme A reductase
(HMGR), the rate-limiting enzyme of mevalonate (MVA) pathway. Besides cholesterol, MVA
pathway leads to the production of several other compounds, which are essential in the regulation of
a plethora of biological activities, including in the central nervous system. For these reasons, statins
are able to induce pleiotropic actions, and acquire increased interest as potential and novel modulators
in brain processes, especially during pathological conditions.
</P><P>
Objective: The purpose of this review is to summarize and examine the current knowledge about
pharmacokinetic and pharmacodynamic properties of statins in the brain. In addition, effects of
statin on brain diseases are discussed providing the most up-to-date information.
</P><P>
Methods: Relevant scientific information was identified from PubMed database using the following
keywords: statins and brain, central nervous system, neurological diseases, neurodegeneration, brain
tumors, mood, stroke.
</P><P>
Results: 315 scientific articles were selected and analyzed for the writing of this review article.
Several papers highlighted that statin treatment is effective in preventing or ameliorating the symptomatology
of a number of brain pathologies. However, other studies failed to demonstrate a neuroprotective
effect.
Conclusion:
Even though considerable research studies suggest pivotal functional outcomes induced
by statin therapy, additional investigation is required to better determine the pharmacological
effectiveness of statins in the brain, and support their clinical use in the management of different
neuropathologies.
Publisher
Bentham Science Publishers Ltd.
Subject
Pharmacology (medical),Psychiatry and Mental health,Neurology (clinical),Neurology,Pharmacology,General Medicine
Reference315 articles.
1. Sirtori CR. Pharmacol Res, The pharmacology of statins.,, 2014, 88,, 3-11,[http://dx.doi.org/10.1016/j.phrs.2014.03.00]. 2. Segatto M, Leboffe L, Trapani L, Pallottini V. Curr Med Chem, Cholesterol homeostasis failure in the brain: implications for synaptic dysfunction and cognitive decline.,, 2014, 21,, 2788-2802,[http://dx.doi.org/10.2174/092986732166614030314290]. 3. Trapani L, Segatto M, Pallottini V. World J Hepatol, Regulation and deregulation of cholesterol homeostasis: The liver as a metabolic “power station”.,, 2012, 4,, 184-190,[http://dx.doi.org/ 10.4254/wjh.v4.i6.]. 4. Espenshade PJ, Hughes AL. Annu Rev Genet, Regulation of sterol synthesis in eukaryotes.,, 2007, 41,, 401-427,[http://dx.doi. org/10.1146/annurev.genet.41.110306.130]. 5. Marino M, di Masi A, Trezza V, Pallottini V, Polticelli F, Ascenzi P. Curr Drug Metab, Xenosensors CAR and PXR at work: impact on statin metabolism.,, 2011, 12,, 300-311,[http://dx. doi.org/10.2174/1389200117951018].
Cited by
76 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|