Version 1
: Received: 5 July 2024 / Approved: 8 July 2024 / Online: 9 July 2024 (12:24:29 CEST)
How to cite:
Shrivastava, P.; Lu, Y.; Su, S.; Kobayashi, Y.; Zhao, Y.; Lien, N.; Masoud, A.-R.; Lukiw, W. J.; Hong, S. Maresin-like 1 Ameliorates Neuropathology of Alzheimer's Disease in Brains of a Transgenic Mouse Model. Preprints2024, 2024070723. https://doi.org/10.20944/preprints202407.0723.v1
Shrivastava, P.; Lu, Y.; Su, S.; Kobayashi, Y.; Zhao, Y.; Lien, N.; Masoud, A.-R.; Lukiw, W. J.; Hong, S. Maresin-like 1 Ameliorates Neuropathology of Alzheimer's Disease in Brains of a Transgenic Mouse Model. Preprints 2024, 2024070723. https://doi.org/10.20944/preprints202407.0723.v1
Shrivastava, P.; Lu, Y.; Su, S.; Kobayashi, Y.; Zhao, Y.; Lien, N.; Masoud, A.-R.; Lukiw, W. J.; Hong, S. Maresin-like 1 Ameliorates Neuropathology of Alzheimer's Disease in Brains of a Transgenic Mouse Model. Preprints2024, 2024070723. https://doi.org/10.20944/preprints202407.0723.v1
APA Style
Shrivastava, P., Lu, Y., Su, S., Kobayashi, Y., Zhao, Y., Lien, N., Masoud, A. R., Lukiw, W. J., & Hong, S. (2024). Maresin-like 1 Ameliorates Neuropathology of Alzheimer's Disease in Brains of a Transgenic Mouse Model. Preprints. https://doi.org/10.20944/preprints202407.0723.v1
Chicago/Turabian Style
Shrivastava, P., Walter J Lukiw and Song Hong. 2024 "Maresin-like 1 Ameliorates Neuropathology of Alzheimer's Disease in Brains of a Transgenic Mouse Model" Preprints. https://doi.org/10.20944/preprints202407.0723.v1
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 effects of long-term treatment with a 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 astrogliosis and microgliosis and the pro-inflammatory M1 polarization of microglia, curbed the AD-associated decline in an-ti-inflammatory Iba1+Arg-1+-M2 microglia, reduced astrogliosis-associated level of neuroin-flammatory TNF-α, inhibited phenotype switching of pro-inflammatory neurotoxic A1 astrocytes and N1 neutrophils, promoted polarization of inflammation-resolving neuroprotective A2 as-trocytes, promoted the blood–brain-barrier-associated tight-junction protein claudin-5 and de-creased neutrophil leakage in 5xFAD brains, and induced the switch of neutrophils toward the inflammation-resolving N2 phenotype. 4) Conclusion: Long-term administration of MarL1 mit-igates AD-related neuropathogenesis in brains by curbing neuroinflammation and neurodegen-eration. These findings provided the preclinical leads and mechanistic insights for the develop-ment of MarL1 into an effective modality to ameliorate AD pathogenesis.
Keywords
Maresin-like; Alzheimer's Disease; neuroinflammation; neuropathogenesis; amyloid-β (Aβ); cholinergic neuron; cleaved-caspase-3; M1 or M2 microglia; A1 or A2 astrocytes; N1 or N2 neutrophil
Subject
Medicine and Pharmacology, Neuroscience and Neurology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
,
,
,
,
,
*
