Autophagy Promotes Microglia Activation Through Beclin-1-Atg5 Pathway in Intracerebral Hemorrhage

Yuan, Bangqing; Shen, Haikang; Lin, Li; Su, Tonggang; Zhong, Lina; Yang, Zhao

doi:10.1007/s12035-015-9642-z

Cited by 41 publications

(26 citation statements)

References 38 publications

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“…Reduced microglia activation is accompanied by reduced levels of proinflammatory cytokines and chemokines and increased levels of anti-inflammatory cytokines, and this might account for the reduced neural stem and progenitor cell death in neuronal Atg7 KO mouse pups or vice versa . Autophagy has important roles in the regulation of microglia activation and inflammation, 44, 45 and the interaction between autophagy and microglia activation needs to be investigated further. 45, 46 …”

Section: Discussionmentioning

confidence: 99%

Inhibition of autophagy prevents irradiation-induced neural stem and progenitor cell death in the juvenile mouse brain

Wang

Zhou

et al. 2017

Cell Death Dis

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Radiotherapy is an effective tool in the treatment of malignant brain tumors. However, damage to brain stem and progenitor cells constitutes a major problem and is associated with long-term side effects. Autophagy has been shown to be involved in cell death, and the purpose of this study was to evaluate the effect of autophagy inhibition on neural stem and progenitor cell death in the juvenile brain. Ten-day-old selective Atg7 knockout (KO) mice and wild-type (WT) littermates were subjected to a single 6Gy dose of whole-brain irradiation. Cell death and proliferation as well as microglia activation and inflammation were evaluated in the dentate gyrus of the hippocampus and in the cerebellum at 6 h after irradiation. We found that cell death was reduced in Atg7 KO compared with WT mice at 6 h after irradiation. The number of activated microglia increased significantly in both the dentate gyrus and the cerebellum of WT mice after irradiation, but the increase was lower in the Atg7 KO mice. The levels of proinflammatory cytokines and chemokines decreased, especially in the cerebellum, in the Atg7 KO group. These results suggest that autophagy might be a potential target for preventing radiotherapy-induced neural stem and progenitor cell death and its associated long-term side effects.

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Section: Discussionmentioning

confidence: 99%

Inhibition of autophagy prevents irradiation-induced neural stem and progenitor cell death in the juvenile mouse brain

Wang

Zhou

et al. 2017

Cell Death Dis

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“…Autophagy is another contributing factor to the secondary injury after ICH. Research indicated that many substances could activate autophagy which caused secondary injury in the brain after ICH [51–53]. We are glad to see that the suppressed autophagy effect of artesunate has been confirmed in in vitro experiment [54].…”

Section: Effect Of Artesunate On Central Nervous System Diseasesmentioning

confidence: 96%

The Potential Therapeutic Effects of Artesunate on Stroke and Other Central Nervous System Diseases

Zuo

Liu

et al. 2016

BioMed Research International

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Artesunate is an important agent for cerebral malaria and all kinds of other severe malaria because it is highly efficient, lowly toxic, and well-tolerated. Loads of research pointed out that it had widespread pharmacological activities such as antiparasites, antitumor, anti-inflammation, antimicrobes activities. As we know, the occurrence and development of neurological disorders usually refer to intricate pathophysiologic mechanisms and multiple etiopathogenesis. Recent progress has also demonstrated that drugs with single mechanism and serious side-effects are not likely the candidates for treatment of the neurological disorders. Therefore, the pluripotent action of artesunate may result in it playing an important role in the prevention and treatment of these neurological disorders. This review provides an overview of primary pharmacological mechanism of artesunate and its potential therapeutic effects on neurological disorders. Meanwhile, we also briefly summarize the primary mechanisms of artemisinin and its derivatives. We hope that, with the evidence presented in this review, the effect of artesunate in prevention and curing for neurological disorders can be further explored and studied in the foreseeable future.

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“…The incidences of ICH bring damage to the brain function, results in cognitive decline or brain injury 4 . The previous experiments have indicated that microglia mediated inflammation contributed to the pathology progress of ICH 5 – 7 .…”

Section: Introductionmentioning

confidence: 96%

Hemoglobin enhances miRNA-144 expression and autophagic activation mediated inflammation of microglia via mTOR pathway

Wang

Yuan

et al. 2017

Sci Rep

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Intracerebral hemorrhage promotes autophagic activation of microglia and enhances neuroinflammation. MiRNAs are key factors to autophagy, contributed to negatively and posttranscriptionally regulate gene expression and function. However, the specific miRNAs involved in the intracerebral hemorrhage mediated microglia autophagic activation are unidentified. In this experiment, microglia was treated with hemoglobin. And then, miRNA-144 expression, autophagic activation and inflammation of microglia were detected. In addition, the mTOR target of miRNA-144 and its regulation were identified. Our data demonstrated that hemoglobin promoted miRNA-144 expression and autophagic activation mediated inflammation. Additionally, miRNA-144 targeted mTOR by directly interacting with the 3′ untranslated regions (UTRs), mutations of the binding sites abolish the miRNA-144 responsiveness. Overexpression of mTOR decreased autophagic activation and inflammation of microglia. Therefore, our results suggested that miRNA-144 contributed to hemoglobin mediated autophagic activation and inflammation of microglia via mTOR pathway. And miRNA based treatment provided novel therapeutical strategy for intracerebral hemorrhage.

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Autophagy Promotes Microglia Activation Through Beclin-1-Atg5 Pathway in Intracerebral Hemorrhage

Cited by 41 publications

References 38 publications

Inhibition of autophagy prevents irradiation-induced neural stem and progenitor cell death in the juvenile mouse brain

Inhibition of autophagy prevents irradiation-induced neural stem and progenitor cell death in the juvenile mouse brain

The Potential Therapeutic Effects of Artesunate on Stroke and Other Central Nervous System Diseases

Hemoglobin enhances miRNA-144 expression and autophagic activation mediated inflammation of microglia via mTOR pathway

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