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Cited by 339Cholesterol and Lipid MetabolismLipoproteins and Cardiovascular HealthLysosomal Storage Disorders Research

Cholesterol: its regulation and role in central nervous system disorders

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Orth, Matthias, Bellosta, Stefano·2012·Cholesterol
DOI 10.1155/2012/292598PMC PMC3483652
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Abstract

Cholesterol is a major constituent of the human brain, and the brain is the most cholesterol-rich organ. Numerous lipoprotein receptors and apolipoproteins are expressed in the brain. Cholesterol is tightly regulated between the major brain cells and is essential for normal brain development. The metabolism of brain cholesterol differs markedly from that of other tissues. Brain cholesterol is primarily derived by de novo synthesis and the blood brain barrier prevents the uptake of lipoprotein cholesterol from the circulation. Defects in cholesterol metabolism lead to structural and functional central nervous system diseases such as Smith-Lemli-Opitz syndrome, Niemann-Pick type C disease, and Alzheimer’s disease. These diseases affect different metabolic pathways (cholesterol biosynthesis, lipid transport and lipoprotein assembly, apolipoproteins, lipoprotein receptors, and signaling molecules). We review the metabolic pathways of cholesterol in the CNS and its cell-specific and microdomain-specific interaction with other pathways such as the amyloid precursor protein and discuss potential treatment strategies as well as the effects of the widespread use of LDL cholesterol-lowering drugs on brain functions.

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  • The beneficial effects of statins in Mecp2-deficient mice presumably reflect mechanisms of action other than inhibition of cholesterol synthesis, given that brain cholesterol synthesis is already moderately suppressed in these mice.

    “As statins were designed to act primarily by inhibiting cholesterol synthesis, their beneficial effects in the Mecp2-deficient mouse presumably reflect other mechanisms of action given that brain cholesterol synthesis is already moderately suppressed in these mice (Orth and Bellosta, 2012; Martin et al., 2014).”

    From Suppression of brain cholesterol synthesis in male Mecp2-deficient mice is age dependent and not accompanied by a concurrent change in the rate of fatty acid synthesis (2017) · cites this paper as Orth and Bellosta, 2012

    Section 7, “Cholesterol Synthesis Inhibitors” (page not provided), says statins primarily inhibit Hmgcr and may affect brain function through pathways other than cholesterol synthesis. It does not address Mecp2-deficient mice, whether their brain cholesterol synthesis is suppressed, or why statins benefit those mice. (LLM, conf=0.88)

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References 239 · Cited by 339

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Authors
Orth, M., & Bellosta, S.
Affiliations
  • Institut für Laboratoriumsmedizin, Vinzenz von Paul Kliniken gGmbH, Adlerstraβe 7, Postfach 103163, 70199 Stuttgart, Germany
  • University of Milan (IT)
Corresponding author
Orth, Matthias
ORCID
Venue
Cholesterol
Publisher
Wiley
Published
2012-10-17
Volume
2012
Pages
1-19
ISSN
  • 2090-1283 (ISSN-L)
  • 2090-1291
DOI
10.1155/2012/292598
PMC
PMC3483652
OpenAlex
W2146219284
Cited by
339
References
239
Citations by year
2026: 20 · 2025: 27 · 2024: 22 · 2023: 36 · 2022: 28 · 2021: 26 · 2020: 23 · 2019: 26 · 2018: 28 · 2017: 24 · 2016: 31 · 2015: 22 · 2014: 20 · 2013: 5
FWCI
15.35
Type
journal article
Language
en
Open access
Licence
Locations
  • Cholesterol (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Archivio Istituzionale della Ricerca (Universita Degli Studi Di Milano) (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • Deutsche Forschungsgemeinschaft (79 1-1, 79/4-2, IZKF TP C16)
  • Interdisciplinary center for Clinical Research, University of Leipzig (79 1-1, 79/4-2, IZKF TP C16)
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Physiology › Lysosomal Storage Disorders Research
Keywords
brain cholesterol, cholesterol metabolism, cholesterol biosynthesis, blood-brain barrier, apolipoproteins, lipoprotein receptors, lipid transport, lipoprotein assembly, Smith-Lemli-Opitz syndrome, Niemann-Pick disease type C, Alzheimer's disease, amyloid precursor protein, central nervous system disorders

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