Pro-Resolving Lipid Mediators Improve Neuronal Survival and Increase Aβ42 Phagocytosis
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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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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)
Experimental — accuracy not yet measuredLC-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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- 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
- 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
- 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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