Document Type
Article
Publication Date
12-17-2024
Publication Title
Biomedicines
Abstract
(1) Background: Impeded resolution of inflammation contributes substantially to the pathogenesis of Alzheimer's disease (AD); consequently, resolving inflammation is pivotal to the amelioration of AD pathology. This can potentially be achieved by the treatment with specialized pro-resolving lipid mediators (SPMs), which should resolve neuroinflammation in brains. (2) Methods: Here, we report the histological effects of long-term treatment with an SPM, maresin-like 1 (MarL1), on AD pathogenesis in a transgenic 5xFAD mouse model. (3) Results: MarL1 treatment reduced Aβ overload, curbed the loss of neurons in brains especially cholinergic neurons associated with cleaved-caspase-3-associated apoptotic degeneration, reduced microgliosis and the pro-inflammatory M1 polarization of microglia, curbed the AD-associated decline in anti-inflammatory Iba1Arg-1-M2 microglia, inhibited phenotypic switching to pro-inflammatory N1 neutrophils, promoted the blood-brain barrier-associated tight-junction protein claudin-5 and decreased neutrophil leakage in 5xFAD brains, and induced the switch of neutrophils toward the inflammation-resolving N2 phenotype. (4) Conclusions: Long-term administration of MarL1 mitigates AD-related neuropathogenesis in brains by curbing neuroinflammation and neurodegeneration, based on the histological results. These findings provide preclinical leads and mechanistic insights for the development of MarL1 into an effective modality to ameliorate AD pathogenesis.
PubMed ID
39767773
Volume
12
Issue
12
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.
Recommended Citation
Shrivastava, Pallavi; Lu, Yan; Su, Shanchun; Kobayashi, Yuichi; Zhao, Yuhai; Lien, Nathan; Masoud, Abdul-Razak; Lukiw, Walter J.; and Hong, Song, "Maresin-like 1 Ameliorates Neuropathology of Alzheimer's Disease in Brains of a Transgenic Mouse Model" (2024). School of Medicine Faculty Publications. 3400.
https://digitalscholar.lsuhsc.edu/som_facpubs/3400
10.3390/biomedicines12122865
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