Cited by 212Fatty Acid Research and HealthAlzheimer's disease research and treatmentsNeuroinflammation and Neurodegeneration Mechanisms

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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

DOI 10.1007/s12035-015-9544-0PMC PMC4824659

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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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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
ORCID: Zhu, Mingqin
Wang, Xiuzhe
Granholm, Ann-Charlotte
Serhan, Charles N.
Schultzberg, Marianne
Venue: Molecular Neurobiology
Publisher: Springer Science and Business Media LLC
Published: 2015-12-09
Volume: 53
Issue: 4
Pages: 2733-2749
ISSN: 0893-7648 (ISSN-L)
1559-1182
DOI: 10.1007/s12035-015-9544-0
PMC: PMC4824659
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: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
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
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › 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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Pro-Resolving Lipid Mediators Improve Neuronal Survival and Increase Aβ42 Phagocytosis

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