ArticleCNS neuroscience & therapeutics2021
Zinc provides neuroprotection by regulating NLRP3 inflammasome through autophagy and ubiquitination in a spinal contusion injury model.
Article in CNS neuroscience & therapeutics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 63 citations in OpenAlex.
- Trace Elements and Depressive Symptoms in Coronary Artery Disease: A Systematic Review of Sparse and Predominantly Indirect Evidence.International journal of molecular sciences · 2026Pooled it
- Scientific landscape of oxidative stress in sarcopenia: from bibliometric analysis to hotspots review.Frontiers in medicine · 2024Pooled it
- Review
- SIX2-Mediated Microglial M2 Polarization and Exosomal miR-3470b Delivery Protect Dopaminergic Neurons in Parkinson's Disease.CNS neuroscience & therapeutics · 2026Article
- Roles and regulatory mechanisms of autophagy in the pathology of spinal cord injury.Burns & trauma · 2026Review
- Zinc alleviates vascular calcification by activating ERK1/2-mediated autophagy.Scientific reports · 2025Article
- Plasma Zinc Levels in Patients with Diabetic Nephropathy: Is there a Relationship with NLRP3 Inflammasome Activation and Renal Prognosis?Biological trace element research · 2025Article
- Total and Free Zinc Dynamics as Biomarkers for Neurological Impairment in Traumatic Spinal Cord Injury.Nutrients · 2025Article
- Exploring Ubiquitination in Spinal Cord Injury Therapy: Multifaceted Targets and Promising Strategies.Neurochemical research · 2025Review
- The relationship between mixed exposure to blood metal and serum neurofilament light chain levels in the general U.S. population: an unsupervised clustering approach.Frontiers in public health · 2025Article
- Loss of DJ-1 alleviates microglia-mediated neuroinflammation in Parkinson's disease via autophagy-lysosomal degradation of NLRP3.Frontiers in immunology · 2025Article
- Microglia and programmed cell death in spinal cord injury: beyond apoptosis.Frontiers in cell and developmental biology · 2025Review
- The Role of Autophagy in Erectile Dysfunction.The world journal of men's health · 2025Review
- Triolein alleviates ischemic stroke brain injury by regulating autophagy and inflammation through the AKT/mTOR signaling pathway.Molecular medicine (Cambridge, Mass.) · 2024Article
- Zinc homeostasis regulates caspase activity and inflammasome activation.PLoS pathogens · 2024Article
- TRIM28 Fosters Microglia Ferroptosis via Autophagy Modulation to Enhance Neuropathic Pain and Neuroinflammation.Molecular neurobiology · 2024Article
- Hyperhomocysteinemia Is Associated With a Myriad of Age-Related Illnesses: A Potential Role for Metal Toxicity.Mayo Clinic proceedings · 2024Article
- Elamipretide reduces pyroptosis and improves functional recovery after spinal cord injury.CNS neuroscience & therapeutics · 2023Article
- Zinc defends against Parthanatos and promotes functional recovery after spinal cord injury through SIRT3-mediated anti-oxidative stress and mitophagy.CNS neuroscience & therapeutics · 2023Article
- Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aimSpinal cord injury (SCI) is a serious disabling injury worldwide, and the excessive inflammatory response it causes plays an important role in secondary injury. Regulating the inflammatory response can be a potential therapeutic strategy for improving the prognosis of SCI. Zinc has been demonstrated to have a neuroprotective effect in experimental spinal cord injury models. In this study, we aimed to explore the neuroprotective effect of zinc through the suppression of the NLRP3 inflammasome.
methodAllen's method was used to establish an SCI model in C57BL/6J mice. The Basso Mouse Scale (BMS), Nissl staining were employed to confirm the protective effect of zinc on neuronal survival and functional recovery in vivo. Western blotting (WB), immunofluorescence (IF), and enzyme-linked immunosorbent assay (ELISA) were used to detect the expression levels of NLRP3 inflammasome and autophagy-related proteins. Transmission electron microscopy (TEM) was used to confirm the occurrence of zinc-induced autophagy. In vitro, lipopolysaccharide (LPS) and ATP polarized BV2 cells to a proinflammatory phenotype. 3-Methyladenine (3-MA) and bafilomycin A1 (BafA1) were chosen to explore the relationship between the NLRP3 inflammasome and autophagy. A coimmunoprecipitation assay was used to detect the ubiquitination of the NLRP3 protein.
resultsOur data showed that zinc significantly promoted motor function recovery after SCI. In vivo, zinc treatment inhibited the protein expression level of NLRP3 while increasing the level of autophagy. These effects were fully validated by the polarization of BV2 cells to a proinflammatory phenotype. The results showed that when 3-MA and BafA1 were applied, the promotion of autophagy by zinc was blocked and that the inhibitory effect of zinc on NLRP3 was reversed. Furthermore, co-IP confirmed that the promotion of autophagy by zinc also activated the protein expression of ubiquitin and suppressed high levels of NLRP3.
conclusionZinc provides neuroprotection by regulating NLRP3 inflammasome through autophagy and ubiquitination after SCI.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.