DW14006 as a direct AMPKα1 activator improves pathology of AD model mice by regulating microglial phagocytosis and neuroinflammation

Lv, Jiajia; Wang, Wei; Zhu, Xialin; Xu, Xiaoju; Yan, Qiuying; Lu, Jian; Shi, Xiaofan; Wang, Zhengyu; Zhou, Jinpei; Huang, Xi; Wang, Jiaying; Duan, Wenhu; Shen, Xu

doi:10.1016/j.bbi.2020.07.041

Cited by 16 publications

(12 citation statements)

References 78 publications

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“…found that suppressing inflammation via AMPKα1/IκB/NF‐κB signaling contributed to reducing amyloid plaque deposition in APP/PS1 mice. [ 70 ] Similarly, we found that Aβ accumulation in the cortex and HPC of 5xFAD mice decreased after attenuating the neuroinflammatory response by reducing ER stress.…”

Section: Discussionmentioning

confidence: 55%

Exosomes Derived from M2 Microglial Cells Modulated by 1070‐nm Light Improve Cognition in an Alzheimer's Disease Mouse Model

Chen,

Bao,

Xing

et al. 2023

Advanced Science

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Near‐infrared photobiomodulation has been identified as a potential strategy for Alzheimer's disease (AD). However, the mechanisms underlying this therapeutic effect remain poorly characterize. Herein, it is illustrate that 1070‐nm light induces the morphological alteration of microglia from an M1 to M2 phenotype that secretes exosomes, which alleviates the β‐amyloid burden to improve cognitive function by ameliorating neuroinflammation and promoting neuronal dendritic spine plasticity. The results show that 4 J cm−2 1070‐nm light at a 10‐Hz frequency prompts microglia with an M1 inflammatory type to switch to an M2 anti‐inflammatory type. This induces secretion of M2 microglial‐derived exosomes containing miR‐7670‐3p, which targets activating transcription factor 6 (ATF6) during endoplasmic reticulum (ER) stress. Moreover, it is found that miR‐7670‐3p reduces ATF6 expression to further ameliorate ER stress, thus attenuating the inflammatory response and protecting dendritic spine integrity of neurons in the cortex and hippocampus of 5xFAD mice, ultimately leading to improvements in cognitive function. This study highlights the critical role of exosomes derive from 1070‐nm light‐modulated microglia in treating AD mice, which may provide a theoretical basis for the treatment of AD with the use of near‐infrared photobiomodulation.

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Section: Discussionmentioning

confidence: 55%

Exosomes Derived from M2 Microglial Cells Modulated by 1070‐nm Light Improve Cognition in an Alzheimer's Disease Mouse Model

Chen,

Bao,

Xing

et al. 2023

Advanced Science

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“…Several in vitro studies also demonstrated that AMPK activation contributed to the M2 M φ polarization and phagocytosis ( Wan et al, 2013 ; Jin et al, 2014 ; Kaiser et al, 2020 ; Seneviratne et al, 2020 ). Consistently, the absence of AMPK- α1, the sole isoform expressed in M φ, impaired the anti-inflammatory and prophagocytic effect of M φ in various brain disorders ( Vaibhav et al, 2018 ; Lv et al, 2020 ).…”

Section: Upstream Regulators For Erythrophagocytosismentioning

confidence: 81%

“…The mechanisms underlying AMPK’s pro-phagocytosis effect are complex. On the one hand, AMPK cooperates with the transcriptional regulators (PPAR γ and Nrf-2), modulating their downstream scavenger receptors including CD36 and Mertk ( Wan et al, 2013 ; Galvan et al, 2014 ; Wang Y. J. et al, 2018 ; Kaiser et al, 2020 ; Lv et al, 2020 ). On the other hand, AMPK promotes the organization of cytoskeleton and the acidification of endosomal-lysosomal system, facilitating the ingestion and digestion of apoptotic cells ( Labuzek et al, 2010 ; Bae et al, 2011 ).…”

Section: Upstream Regulators For Erythrophagocytosismentioning

confidence: 99%

Erythrophagocytosis by Microglia/Macrophage in Intracerebral Hemorrhage: From Mechanisms to Translation

Liu

Zhu

Leung

2022

Front. Cell. Neurosci.

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Intracerebral hemorrhage (ICH) is a devastating condition characterized by hematoma related mass effect. Microglia/macrophage (M φ) are rapidly recruited in order to remove the red blood cells through erythrophagocytosis. Efficient erythrophagocytosis can detoxify hemolytic products and facilitate neurological recovery after ICH. The underlying mechanisms include modulation of inflammatory response and oxidative stress, among others. It is a dynamic process mediated by a cascade of signal transduction, including “find-me” signals, “eat-me” signals and a set of phagocytotic receptors-ligand pairs that may be exploited as therapeutic targets. This review summarizes mechanistic signaling pathways of erythrophagocytosis and highlights the potential of harnessing M φ-mediated phagocytosis for ICH treatment.

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“…The assay was performed as previously described ( Lv et al, 2020 ). Briefly, after over 5 consecutive days with three trials per day, mice were trained to use a variety of visual cues located on the pool wall to find a hidden submerged white platform in a circular pool (120 cm in diameter, 50 cm deep) filled with milk-tinted water.…”

Section: Methodsmentioning

confidence: 99%

DW14006 as a direct AMPKα1 activator improves pathology of AD model mice by regulating microglial phagocytosis and neuroinflammation

Cited by 16 publications

References 78 publications

Exosomes Derived from M2 Microglial Cells Modulated by 1070‐nm Light Improve Cognition in an Alzheimer's Disease Mouse Model

Exosomes Derived from M2 Microglial Cells Modulated by 1070‐nm Light Improve Cognition in an Alzheimer's Disease Mouse Model

Erythrophagocytosis by Microglia/Macrophage in Intracerebral Hemorrhage: From Mechanisms to Translation

Miltefosine as a PPM1A activator improves AD-like pathology in mice by alleviating tauopathy via microglia/neurons crosstalk

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