ArticleCell & bioscience2022
SENP6 induces microglial polarization and neuroinflammation through de-SUMOylation of Annexin-A1 after cerebral ischaemia-reperfusion injury.
Article in Cell & bioscience, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 44 citations in OpenAlex.
- Post-translational modifications in Neuroimmune cells during neuroinflammation: integrated regulatory networks and therapeutic opportunities.Biology direct · 2026Review
- SENP6-mediated desumoylation of SMAD5 regulates osteogenic fate in periodontal ligament stem cells.European journal of medical research · 2026Article
- SENP6 Maintains Mitochondrial Homeostasis by Regulating Mitochondrial Protein Import Through deSUMOylation of TOM40.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Polyamination with spermidine enhances pathogenic tau conformations while reducing filamentous aggregate formation in vitro.The Biochemical journal · 2025Article
- SENP6-Mediated deSUMOylation of Nrf2 Exacerbates Neuronal Oxidative Stress Following Cerebral Ischemia and Reperfusion Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Regulation of the immune microenvironment by SUMO in diabetes mellitus.Frontiers in immunology · 2025Review
- SENP6 restricts the IFN-I-induced signaling pathway and antiviral activity by deSUMOylating USP8.Cellular & molecular immunology · 2024Article
- Integrating single-nucleus RNA sequencing and spatial transcriptomics to elucidate a specialized subpopulation of astrocytes, microglia and vascular cells in brains of mouse model of lipopolysaccharide-induced sepsis-associated encephalopathy.Journal of neuroinflammation · 2024Article
- The Sirtuin 5 Inhibitor MC3482 Ameliorates Microglia‑induced Neuroinflammation Following Ischaemic Stroke by Upregulating the Succinylation Level of Annexin-A1.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Annexin A1 in the nervous and ocular systems.Neural regeneration research · 2024Review
- Genomic insights into adaptation and inbreeding among Sub-Saharan African cattle from pastoral and agropastoral systems.Frontiers in genetics · 2024Article
- Gene therapy of adeno-associated virus (AAV) vectors in preclinical models of ischemic stroke.CNS neuroscience & therapeutics · 2023Review
- Article
- SENP3-mediated deSUMOylation of c-Jun facilitates microglia-induced neuroinflammation after cerebral ischemia and reperfusion injury.iScience · 2023Article
- TRIM67 alleviates cerebral ischemia‒reperfusion injury by protecting neurons and inhibiting neuroinflammation via targeting IκBα for K63-linked polyubiquitination.Cell & bioscience · 2023Article
- The role of SUMOylation in the neurovascular dysfunction after acquired brain injury.Frontiers in pharmacology · 2023Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundPrevious data have reported that Sentrin/SUMO-specific protease 6 (SENP6) is involved in ischaemic brain injury and induces neuronal apoptosis after cerebral ischaemia, but the role of SENP6 in microglia-induced neuroinflammation and its underlying mechanism remain poorly understood. This research systematically explored the function and potential mechanism of SENP6 in microglia-induced neuroinflammation after ischaemic stroke.
resultsWe first identified an increased protein level of SENP6 in microglia after cerebral ischaemia. Then, we demonstrated that SENP6 promoted detrimental microglial phenotype polarization. Specifically, SENP6-mediated de-SUMOylation of ANXA1 targeted the IκB kinase (IKK) complex and selectively inhibited the autophagic degradation of IKKα in an NBR1-dependent manner, activating the NF-κB pathway and enhancing proinflammatory cytokine expression. In addition, downregulation of SENP6 in microglia effectively reduced cocultured neuronal damage induced by ischaemic stroke. More importantly, we employed an AAV-based technique to specifically knockdown SENP6 in microglia/macrophages, and in vivo experiments showed that SENP6 inhibition in microglia/macrophages notably lessened brain ischaemic infarct size, decreased neurological deficit scores, and ameliorated motor and cognitive function in mice subjected to cerebral ischaemia surgery.
conclusionWe demonstrated a previously unidentified mechanism by which SENP6-mediated ANXA1 de-SUMOylation regulates microglial polarization and our results strongly indicated that in microglia, inhibition of SENP6 may be a crucial beneficial therapeutic strategy for ischaemic stroke.
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