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Cited by 116Lipoproteins and Cardiovascular HealthCancer, Lipids, and MetabolismNeurological Disorders and Treatments

Statins and the Brain: More than Lipid Lowering Agents?

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Fracassi, Anna, Marangoni, Martina, Rosso, Pamela, Pallottini, Valentina, Fioramonti, Marco, Siteni, Silvia, Segatto, Marco·2018·Current Neuropharmacology
DOI 10.2174/1570159x15666170703101816PMC PMC6341496
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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. 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. 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. 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.

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  • The synthesis of cholesterol in the CNS is assured by the mevalonate pathway, which starts from acetate and comprises about 30 enzymatic reactions.

    “The synthesis of this lipid is assured by the so-called mevalonate (MVA) pathway [14] that starts from acetate and comprises a series of ~30 enzymatic reactions.”

    From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [14]

    The Introduction identifies the mevalonate pathway as a major source of cholesterol, and the Cholesterol section says de novo synthesis supplies practically all cholesterol in the CNS (page numbers unavailable). Our copy does not state that the pathway starts from acetate or comprises approximately 30 enzymatic reactions. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • Several diseases including Alzheimer, Huntington, and Parkinson diseases are thought to involve changes in cholesterol metabolism although a direct link cannot be established.

    “Several diseases including Alzheimer, Huntington, and Parkinson diseases are thought to involve changes in cholesterol metabolism although a direct link cannot be established [14] (Table 1).”

    From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [14]

    The Alzheimer’s Disease and Huntington’s Disease sections link both conditions to altered cholesterol metabolism. The Parkinson’s Disease section reports an association between total cholesterol level and Parkinson’s risk, but does not establish altered cholesterol metabolism in Parkinson’s disease. Its uncertainty concerns that association and statin effects, rather than a direct link across all three diseases; page numbers are unavailable in our copy. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Our studies support an involvement of cholesterol metabolism in RTT patients harboring mutations in the Mecp2 gene.

    “Our studies support an involvement of cholesterol metabolism in RTT patients harboring mutations in Mecp2 gene [14,75].”

    From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [14]

  • MeCP2 plays a key role in gene silencing through methylation-dependent remodeling of chromatin structure, and suppresses gene transcription through association with several co-repressors.

    “This protein plays a key role in gene silencing through methylation-dependent remodeling of chromatin structure, and suppresses gene transcription through the association with several co-repressors [14].”

    From Loss of Mevalonate/Cholesterol Homeostasis in the Brain: A Focus on Autism Spectrum Disorder and Rett Syndrome (2019) · cites this paper as [14]

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References 326 · Cited by 116

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200 of 273 shown

Authors
Fracassi, A., Marangoni, M., Rosso, P., Pallottini, V., Fioramonti, M., Siteni, S., & Segatto, M.
Affiliations
  • Department of Science, University of Rome , Italy
  • Medical Genetics Unit, University Hospital of Rome , Italy
  • Université Libre de Bruxelles (BE)
  • Sapienza University of Rome (IT)
Corresponding author
Segatto, Marco
ORCID
Venue
Current Neuropharmacology
Publisher
Bentham Science Publishers Ltd.
Published
2018-12-05
Volume
17
Issue
1
Pages
59-83
ISSN
1570-159X (ISSN-L)
DOI
10.2174/1570159x15666170703101816
PMC
PMC6341496
OpenAlex
W2726472716
Cited by
116
References
326
Citations by year
2026: 13 · 2025: 15 · 2024: 16 · 2023: 19 · 2022: 15 · 2021: 24 · 2020: 9 · 2019: 2 · 2018: 2 · 2016: 1
FWCI
0.75
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Current Neuropharmacology (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
  • Archivio Istituzionale della Ricerca - Università degli Studi del Molise (submittedVersion)
  • IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
  • Iris (Roma Tre University) (submittedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
  • Life Sciences › Neuroscience › Neurology › Neurological Disorders and Treatments
Keywords
statins, brain, central nervous system, mevalonate pathway, HMG-CoA reductase inhibition, pleiotropy, neuroprotection, neurodegeneration, brain tumors, mood, stroke, pharmacokinetics, pharmacodynamics
MeSH terms
Animals, Brain, Brain Diseases, Humans, Randomized Controlled Trials as Topic, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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