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Apolipoprotein E - A Multifunctional Protein with Implications in Various Pathologies as a Result of Its Structural Features

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Tudorache, Irina Florina, Trusca, Violeta Georgeta, Gafencu, Anca Violeta·2017·Computational and Structural Biotechnology Journal
DOI 10.1016/j.csbj.2017.05.003PMC PMC5476973
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Abstract

Apolipoprotein E (apoE), a 34 kDa glycoprotein, mediates hepatic and extrahepatic uptake of plasma lipoproteins and cholesterol efflux from lipid-laden macrophages. In humans, three structural different apoE isoforms occur, with subsequent functional changes and pathological consequences. Here, we review data supporting the involvement of apoE structural domains and isoforms in normal and altered lipid metabolism, cardiovascular and neurodegenerative diseases, as well as stress-related pathological states. Studies using truncated apoE forms provided valuable information regarding the regions and residues responsible for its properties. ApoE3 renders protection against cardiovascular diseases by maintaining lipid homeostasis, while apoE2 is associated with dysbetalipoproteinemia. ApoE4 is a recognized risk factor for Alzheimer's disease, although the exact mechanism of the disease initiation and progression is not entirely elucidated. ApoE is also implicated in infections with herpes simplex type-1, hepatitis C and human immunodeficiency viruses. Interacting with both viral and host molecules, apoE isoforms differently interfere with the viral life cycle. ApoE exerts anti-inflammatory effects, switching macrophage phenotype from the proinflammatory M1 to the anti-inflammatory M2, suppressing CD4+ and CD8+ lymphocytes, and reducing IL-2 production. The anti-oxidative properties of apoE are isoform-dependent, modulating the levels of various molecules (Nrf2 target genes, metallothioneins, paraoxonase). Mimetic peptides were designed to exploit apoE beneficial properties. The "structure correctors" which convert apoE4 into apoE3-like molecules have pharmacological potential. Despite no successful strategy is yet available for apoE-related disorders, several promising candidates deserve further improvement and exploitation.

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  • ApoE combined with triglycerides and cholesterol forms lipoproteins and plays a central role in lipoprotein metabolism.

    “ApoE combined with triglycerides and cholesterol forms lipoproteins and plays a central role in lipoprotein metabolism [11].”

    From Focal segmental glomerulosclerosis with heterozygous apolipoprotein E5 (Glu3Lys) (2018) · cites this paper as [11]

    The Introduction says apoE is associated with nearly all plasma lipoprotein particles and is mainly involved in lipid metabolism. The Lipid Metabolism and Cardiovascular Disorders section says lipidation of apoE can generate HDL and describes its binding to triglyceride-rich VLDL. It does not specifically say that apoE combines with both triglycerides and cholesterol to form lipoproteins. (LLM, conf=0.80)

    Experimental — accuracy not yet measured

  • In previous studies on LPG, osmiophilic granular substances were reported in the subendothelial and mesangial areas.

    “In previous studies on LPG, osmiophilic granular substances were reported in the subendothelial and mesangial areas [10, 11, 12], and one of them showed ApoE deposition and microbubbles like in the current case [10].”

    From Membranous Nephropathy-Like Apolipoprotein E Deposition Disease with Apolipoprotein E Toyonaka (Ser197Cys) and a Homozygous Apolipoprotein E2/2 (2018) · cites this paper as [11]

    The Lipid Metabolism and Cardiovascular Disorders section describes LPG and glomerular lipoprotein thrombi, but does not describe osmiophilic granular substances or their location. Searches for the distinctive phrase and for subendothelial or mesangial deposits found no passage addressing that observation. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

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Authors
Tudorache, I. F., Trusca, V. G., & Gafencu, A. V.
Affiliations
Romanian Academy (RO)
Corresponding author
Gafencu, Anca Violeta
ORCID
Venue
Computational and Structural Biotechnology Journal
Publisher
American Association for the Advancement of Science (AAAS)
Published
2017-01
Volume
15
Pages
359-365
ISSN
2001-0370 (ISSN-L)
DOI
10.1016/j.csbj.2017.05.003
PMC
PMC5476973
OpenAlex
W2624439161
Cited by
186
References
7
Citations by year
2026: 18 · 2025: 23 · 2024: 11 · 2023: 21 · 2022: 24 · 2021: 27 · 2020: 27 · 2019: 17 · 2018: 15 · 2017: 2 · 2012: 1
FWCI
3.51
Type
journal article
Language
en
Open access
Licence
Locations
  • Computational and Structural Biotechnology Journal (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Unitatea Executiva pentru Finantarea Invatamantului Superior, a Cercetarii, Dezvoltarii si Inovarii (PN-II-RU-TE-2014-4-2143, PN-II-RU-TE-2014-4-2660)
  • Corporation for National and Community Service
  • Autoritatea Natională pentru Cercetare Stiintifică
  • Academia Româna
Topics
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
Keywords
apolipoprotein E, APOE isoforms, APOE ε4, APOE3, APOE2, dysbetalipoproteinemia, Alzheimer's disease, cardiovascular disease, lipid metabolism, cholesterol efflux, macrophage polarization, anti-inflammatory activity, oxidative stress, Nrf2, metallothionein, paraoxonase, viral infection, herpes simplex virus type 1, hepatitis C virus, HIV, peptidomimetics

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

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