Cited by 204Fatty Acid Research and HealthAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

Pro-Resolving Lipid Mediators Improve Neuronal Survival and Increase Aβ42 Phagocytosis

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Zhu, Mingqin, Wang, Xiuzhe, Hjorth, Erik, Colas, Romain A., Schroeder, Lisa, Granholm, Ann-Charlotte, Serhan, Charles N., Schultzberg, Marianne·2016·Molecular Neurobiology

Abstract

Inflammation in the brain is a prominent feature in Alzheimer's disease (AD). Recent studies suggest that chronic inflammation can be a consequence of failure to resolve the inflammation. Resolution of inflammation is mediated by a family of lipid mediators (LMs), and the levels of these specialized pro-resolving mediators (SPMs) are reduced in the hippocampus of those with AD. In the present study, we combined analysis of LMs in the entorhinal cortex (ENT) from AD patients with in vitro analysis of their direct effects on neurons and microglia. We probed ENT, an area affected early in AD pathogenesis, by liquid chromatography-tandem mass spectrometry (LC-MS-MS), and found that the levels of the SPMs maresin 1 (MaR1), protectin D1 (PD1), and resolvin (Rv) D5, were lower in ENT of AD patients as compared to age-matched controls, while levels of the pro-inflammatory prostaglandin D2 (PGD2) were higher in AD. In vitro studies showed that lipoxin A4 (LXA4), MaR1, resolvin D1 (RvD1), and protectin DX (PDX) exerted neuroprotective activity, and that MaR1 and RvD1 down-regulated β-amyloid (Aβ)42-induced inflammation in human microglia. MaR1 exerted a stimulatory effect on microglial uptake of Aβ42. Our findings give further evidence for a disturbance of the resolution pathway in AD, and indicate that stimulating this pathway is a promising treatment strategy for AD.

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Crossref · 10.1007/s12035-015-9544-0

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  • In vitro and in vivo studies suggested that MaR1 can inhibit inflammation and promote phagocytosis in microglia and improve cognitive decline in an AD mouse model.

    “In vitro and in vivo studies suggested that MaR1 can inhibit inflammation and promote phagocytosis in microglia428,430,431 and improve the cognitive decline in AD mouse model.432”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [428]

    The Discussion reports that MaR1 stimulated Aβ42 phagocytosis and reduced pro-inflammatory markers in cultured human microglia, supporting the in vitro part of the cited clause. This paper does not show those MaR1 effects in vivo. The mouse-cognition claim has a separate citation in the printed sentence and is not assessed against this source. (LLM, conf=0.84)

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  • LC-MS-MS analysis of lipid mediators in the entorhinal cortex of AD patients revealed downregulation of SPMs including PD1, MaR1 and RvD5, and upregulation of PGD2 compared with age-matched controls.

    “Liquid chromatography-tandem mass spectrometry (LC-MS-MS) analysis of lipid mediators in the entorhinal cortex of AD patients revealed the downregulation of SPMs including protectin D1 (PD1), maresin 1 (MaR1) and resolvin (RvD5), and upregulation of PGD2, a proinflammatory lipid mediator, compared with age-matched controls.428”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [428]

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1 of the 90 references couldn’t be matched to a known paper.

Research works printed but not linked: 4

  1. [22]Serhan CN Hong S Gronert K Colgan SP Devchand PR Mirick G Moussignac RL Resolvins: a family of bioactive products of omega-3 fatty acid transformation circuits initiated by aspirin treatment that counter proinflammation signals J Exp Med 2002 196 8 1025 1037 12391014 PMC2194036
  2. [25]Xu ZZ Liu XJ Berta T Park CK Lu N Serhan CN Ji RR NpD/PD1 protects against neuropathic pain in mice after nerve trauma Annals of Neurology 2013 74 3 490 495 23686636 PMC3791159
  3. [38]Zhu M Wang X Hjorth E Schultzberg M Differential regulation of resolution in inflammation induced by Aβ42 and LPS in human microglia J Alzheimers Dis 2015 43 1237 1250 25147114
  4. [87]Dalli J Zhu M Vlasenko NA Deng B Haeggstrom JZ Petasis NA Serhan CN The novel 13S,14S–epoxy-maresin is converted by human macrophages to maresin 1 (MaR1), inhibits leukotriene A4 hydrolase (LTA4H), and shifts macrophage phenotype FASEB J 2013 27 7 2573 2583 23504711 PMC3688739

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Authors
Zhu, M., Wang, X., Hjorth, E., Colas, R. A., Schroeder, L., Granholm, A.-C., Serhan, C. N., & Schultzberg, M.
Affiliations
  • Karolinska Institutet (SE)
  • Shanghai Jiao Tong University (CN)
  • Brigham and Women's Hospital (US)
  • Medical University of South Carolina (US)
Corresponding author
Schultzberg, Marianne
Venue
Molecular Neurobiology
Published
2015-12-09
Volume
53
Issue
4
Pages
2733-2749
ISSN
  • 0893-7648 (ISSN-L)
  • 1559-1182
OpenAlex
W2291813090
Cited by
204
References
90
Citations by year
2026: 14 · 2025: 10 · 2024: 22 · 2023: 21 · 2022: 25 · 2021: 26 · 2020: 20 · 2019: 21 · 2018: 19 · 2017: 20 · 2016: 6
FWCI
14.46
Type
journal article
Language
en
Open access
Locations
  • Molecular Neurobiology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • The Swedish Research Council (22743 and 22744)
  • The Chinese Scholarship Council
  • Swedish Brain Power
  • The Knut and Alice Wallenberg Foundation
  • Karolinska Institutet research funds
  • The Swedish Alzheimer Foundation
  • Stiftelsen för Gamla Tjänarinnor
  • Gun och Bertil Stohnes Stiftelse
  • Barmore Fund
  • National Institutes of Health (P01GM095467, GM038765)
Topics
  • Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
  • Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
Alzheimer's disease, inflammation resolution, specialized pro-resolving mediators, lipid mediators, entorhinal cortex, maresin 1, protectin D1, resolvin D1, lipoxin A4, protectin DX, resolvin D5, prostaglandin D2, microglia, amyloid-beta 42, phagocytosis, neuroprotection, neuroinflammation
MeSH terms
Aged, Cell Survival, Chromatography, Liquid, Female, Humans, Lipids, Male, Neurons, Peptide Fragments, Phagocytosis, Phenotype, Postmortem Changes, Amyloid beta-Peptides, Microglia, Entorhinal Cortex, Staurosporine, Cell Line, Tumor, Tandem Mass Spectrometry

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