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Cited by 686Cholesterol and Lipid MetabolismAlzheimer's disease research and treatmentsCancer, Lipids, and Metabolism

Cholesterol metabolism and homeostasis in the brain

Open access
Zhang, Juan, Liu, Qiang·2015·Protein & Cell
DOI 10.1007/s13238-014-0131-3PMC PMC4383754
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Abstract

Cholesterol is an essential component for neuronal physiology not only during development stage but also in the adult life. Cholesterol metabolism in brain is independent from that in peripheral tissues due to blood-brain barrier. The content of cholesterol in brain must be accurately maintained in order to keep brain function well. Defects in brain cholesterol metabolism has been shown to be implicated in neurodegenerative diseases, such as Alzheimer's disease (AD), Huntington's disease (HD), Parkinson's disease (PD), and some cognitive deficits typical of the old age. The brain contains large amount of cholesterol, but the cholesterol metabolism and its complex homeostasis regulation are currently poorly understood. This review will seek to integrate current knowledge about the brain cholesterol metabolism with molecular mechanisms.

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  • Secreted ApoE is generally presumed to be converted into HDL-like LNPs by astrocytes.

    “As the major lipid carrier in the brain, secreted ApoE is generally presumed to be converted into HDL-like LNPs by astrocytes.”

    From ApoE is Secreted as a Lipid Nanoparticle by Mammalian Cells: Implications for Alzheimer’s Disease Pathogenesis (2025) · cites this paper as [45]

    The “Apolipoproteins (apoE) in the brain” section (page unavailable) identifies astrocytes as the major source of ApoE and says glial cells secrete ApoE-containing lipoproteins. The “Lipoprotein Lipidation” section describes ApoE being lipidated to form particles, but our copy does not say that secreted ApoE is subsequently converted by astrocytes into HDL-like particles. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • These LNPs undergo receptor-mediated endocytosis in neurons and glia cells where their lipid constituents are disassembled in lysosomes to supply these constituents to recipient cells.

    “In turn, these LNPs undergo receptor-mediated endocytosis in neurons and glia cells where their lipid constituents are disassembled in lysosomes to supply these constituents to the recipient cells.22, 44–47”

    From ApoE is Secreted as a Lipid Nanoparticle by Mammalian Cells: Implications for Alzheimer’s Disease Pathogenesis (2025) · cites this paper as [45]

    The Cholesterol Homeostasis section describes receptor-mediated uptake of apoE-containing lipoproteins by neurons, followed by processing of their cholesterol in lysosomes for delivery to membranes. The LDL receptor family section describes uptake receptors in both neurons and glia. The paper does not establish that all lipid constituents of these particles are disassembled in lysosomes, or explicitly describe that full sequence in glial cells. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • Cholesterol reduction in neurons impairs synaptic vesicle exocytosis, neuronal activity, and neurotransmission and leads to dendritic spine and synapse degradation.

    “Cholesterol reduction in neurons impairs synaptic vesicle exocytosis, neuronal activity, and neurotransmission and leads to dendritic spine and synapse degradation [20].”

    From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [20]

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Authors
Zhang, J., & Liu, Q.
Affiliations
University of Science and Technology of China (CN)
Corresponding author
Liu, Qiang
ORCID
Venue
Protein & Cell
Publisher
Oxford University Press (OUP)
Published
2015-02-15
Volume
6
Issue
4
Pages
254-264
ISSN
  • 1674-800X (ISSN-L)
  • 1674-8018
DOI
10.1007/s13238-014-0131-3
PMC
PMC4383754
OpenAlex
W1990008286
Cited by
686
References
13
Citations by year
2026: 65 · 2025: 78 · 2024: 77 · 2023: 83 · 2022: 72 · 2021: 79 · 2020: 68 · 2019: 56 · 2018: 49 · 2017: 36 · 2016: 18 · 2015: 4
FWCI
6.83
Type
journal article
Language
en
Open access
Licence
Locations
  • Protein & Cell (publishedVersion, cc-by-nc)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Natural Science Foundation of China (973 Program, 31371087, 91332111, 81422015)
  • National Key Research and Development Program of China (2014CB548100)
  • Fundamental Research Funds for the Central Universities
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Keywords
brain cholesterol metabolism, cholesterol homeostasis, blood-brain barrier, neurodegenerative diseases, Alzheimer's disease, Huntington's disease, Parkinson's disease, cognitive impairment, neuronal physiology, molecular mechanisms
MeSH terms
Alzheimer Disease, Blood-Brain Barrier, Brain, Cholesterol, Gene Expression Regulation, Homeostasis, Humans, Huntington Disease, Hydroxycholesterols, Neurons, Parkinson Disease, Receptors, Lipoprotein, ATP-Binding Cassette Transporters, Lipid Metabolism

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