Polygala saponins inhibit NLRP3 inflammasome-mediated neuroinflammation via SHP-2-Mediated mitophagy

Qiu, Wen-Qiao; Ai, Wei; Zhu, Feng-Dan; Zhang, Yue; Guo, Min-Song; Law, Betty Yuen‐Kwan; Wu, Jianming; Wong, Vincent Kam‐Wai; Tang, Yong; Yu, Lu; Chen, Qi; Yu, Chong-Lin; Liu, Jian; Qin, Da-Lian; Zhou, Xiao-Gang; Wu, Anguo

doi:10.1016/j.freeradbiomed.2021.12.263

Cited by 47 publications

(19 citation statements)

References 52 publications

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“…SHP2 is a protein‐tyrosine phosphatases that induces mitophagy by upregulating its expression or activation. [ 19,21 ] The SHP2 protein can act as biological drug for AD treatment. However, due to the poor stability, difficulty in separation and purification, and poor blood–brain penetration efficacy, the SHP2 protein can hardly be used in clinical practice.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, polygala saponins inhibit NLRP3 inflammasome‐mediated neuroinflammation via the upregulation of SHP2, and lovastatin alleviates Parkinsonism by boosting SHP2‐mediated mitophagy. [ 19–21 ] Therefore, we hypothesize that the improvement of AD can be realized by increasing SHP2‐mediated mitophagy. However, the high toxicity and low enrichment in the brain of the existing autophagy inducers or compounds for SHP2‐mediated mitophagy significantly limit their research and the future clinical transformation applications for AD therapy.…”

Section: Introductionmentioning

confidence: 99%

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Engineered Extracellular Vesicles with SHP2 High Expression Promote Mitophagy for Alzheimer's Disease Treatment

Yang

Cheng

et al. 2022

Advanced Materials

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Mitochondrial dysfunction is a fundamental pathological feature of Alzheimer's disease (AD). However, toxicity and poor brain enrichment of existing mitophagy inducers limit their further applications. In this study, a platform for AD therapy is developed using nanosized mesenchymal‐stem‐cells‐derived extracellular vesicles with tyrosine phosphatase‐2 (SHP2) high‐expression (MSC‐EVs‐SHP2). The high blood–brain barrier penetration ability of MSC‐EVs‐SHP2 is demonstrated in AD‐mice, facilitating SHP2 delivery to the brain. In addition, MSC‐EVs‐SHP2 significantly induces mitophagy of neuronal cells, which alleviates mitochondrial damage‐mediated apoptosis and NLRP3 inflammasome activation. Mitophagy further diminishes neuronal cells apoptosis and neuroinflammation, culminating with rescued synaptic loss and cognitive decline in an AD mouse model. The EV‐engineering technology provides a potential platform for effective AD therapy by inducing mitophagy.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Engineered Extracellular Vesicles with SHP2 High Expression Promote Mitophagy for Alzheimer's Disease Treatment

Yang

Cheng

et al. 2022

Advanced Materials

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“…DJ-1 interference combined with a Sirt1 inhibitor increased the effect of DJ-1 interference on microglial polarization from anti-inflammatory to pro-inflammatory states, decreased the level of the Atg5-Atg12-Atg16L1 complex, and inhibited autophagy during cerebral I/R injury (170). Activation of autophagy via the AMPK pathway could facilitate microglial anti-inflammatory activation and exert neuroprotective effects during an inflammatory process (171)(172)(173)(174)(175). P2X7 receptor can activate AMPK pathways in the regulation of mitochondrial and lysosomal functions in microglia (176,177).…”

Section: Microglia Autophagy Regulates Inflammatory Responses In Isch...mentioning

confidence: 99%

Microglia autophagy in ischemic stroke: A double-edged sword

Peng

Yao

et al. 2022

Front. Immunol.

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Ischemic stroke (IS) is one of the major types of cerebrovascular diseases causing neurological morbidity and mortality worldwide. In the pathophysiological process of IS, microglia play a beneficial role in tissue repair. However, it could also cause cellular damage, consequently leading to cell death. Inflammation is characterized by the activation of microglia, and increasing evidence showed that autophagy interacts with inflammation through regulating correlative mediators and signaling pathways. In this paper, we summarized the beneficial and harmful effects of microglia in IS. In addition, we discussed the interplay between microglia autophagy and ischemic inflammation, as along with its application in the treatment of IS. We believe this could help to provide the theoretical references for further study into IS and treatments in the future.

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“…In turn, activated glial cells release inflammatory factors, triggering cellular cascades, which can exacerbate mitochondrial damage, triggering and intensifying a vicious circle between neuroinflammation and mitochondrial dysfunction, which finally results in NDD. Notably, mitochondrial quality control by mitophagy is a crucial intrinsic response to prevent neuroinflammation, by limiting mtDNA and mtROS release from damaged mitochondria, and NLRP3 inflammasome activation [ 234 , 235 , 236 , 237 ].…”

Section: Neuroprotective Potential Of β-Caryophyllene and Carnosic Ac...mentioning

confidence: 99%

Multi-Target Effects of ß-Caryophyllene and Carnosic Acid at the Crossroads of Mitochondrial Dysfunction and Neurodegeneration: From Oxidative Stress to Microglia-Mediated Neuroinflammation

2022

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Inflammation and oxidative stress are interlinked and interdependent processes involved in many chronic diseases, including neurodegeneration, diabetes, cardiovascular diseases, and cancer. Therefore, targeting inflammatory pathways may represent a potential therapeutic strategy. Emerging evidence indicates that many phytochemicals extracted from edible plants have the potential to ameliorate the disease phenotypes. In this scenario, ß-caryophyllene (BCP), a bicyclic sesquiterpene, and carnosic acid (CA), an ortho-diphenolic diterpene, were demonstrated to exhibit anti-inflammatory, and antioxidant activities, as well as neuroprotective and mitoprotective effects in different in vitro and in vivo models. BCP essentially promotes its effects by acting as a selective agonist and allosteric modulator of cannabinoid type-2 receptor (CB2R). CA is a pro-electrophilic compound that, in response to oxidation, is converted to its electrophilic form. This can interact and activate the Keap1/Nrf2/ARE transcription pathway, triggering the synthesis of endogenous antioxidant “phase 2” enzymes. However, given the nature of its chemical structure, CA also exhibits direct antioxidant effects. BCP and CA can readily cross the BBB and accumulate in brain regions, giving rise to neuroprotective effects by preventing mitochondrial dysfunction and inhibiting activated microglia, substantially through the activation of pro-survival signalling pathways, including regulation of apoptosis and autophagy, and molecular mechanisms related to mitochondrial quality control. Findings from different in vitro/in vivo experimental models of Parkinson’s disease and Alzheimer’s disease reported the beneficial effects of both compounds, suggesting that their use in treatments may be a promising strategy in the management of neurodegenerative diseases aimed at maintaining mitochondrial homeostasis and ameliorating glia-mediated neuroinflammation.

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Polygala saponins inhibit NLRP3 inflammasome-mediated neuroinflammation via SHP-2-Mediated mitophagy

Cited by 47 publications

References 52 publications

Engineered Extracellular Vesicles with SHP2 High Expression Promote Mitophagy for Alzheimer's Disease Treatment

Engineered Extracellular Vesicles with SHP2 High Expression Promote Mitophagy for Alzheimer's Disease Treatment

Microglia autophagy in ischemic stroke: A double-edged sword

Multi-Target Effects of ß-Caryophyllene and Carnosic Acid at the Crossroads of Mitochondrial Dysfunction and Neurodegeneration: From Oxidative Stress to Microglia-Mediated Neuroinflammation

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