ArticleJournal of neuroinflammation2025
SIK2 mediated mitochondrial homeostasis in spinal cord injury: modulating oxidative stress and the AIM2 inflammasome via CRTC1/CREB signaling.
Article in Journal of neuroinflammation, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed.
- Ferroptosis-Pyroptosis Crosstalk in Spinal Cord Injury: Molecular Mechanisms, Emerging Connectors, and Staged Therapeutic Perspectives.Journal of molecular neuroscience : MN · 2026Review
- Transplantation of LPS, IL-4, and TGF-β-induced reparative-biased macrophages promotes early motor functional recovery after spinal cord injury in rats.Journal of orthopaedic translation · 2026Article
- Mitochondrial homeostasis imbalance-triggered PANoptosis in traumatic brain and spinal cord injury: from mechanism to therapeutic strategies.Redox biology · 2026Review
- hUC-MSCs transplantation promotes neurological recovery by ameliorating spinal cord injury and hippocampal synaptic remodeling in female mice.Journal of orthopaedic translation · 2026Article
- Potential Role of Mitochondria-Associated Endoplasmic Reticulum Membranes (MAMs) Abnormalities in Epileptogenesis: Multimodal Mechanisms and Therapeutic Targets.Molecular neurobiology · 2026Review
- The Protective Effects of Chlorogenic Acid in Mitigating Gut-Brain Barrier Dysfunction and Autism-Like Symptoms Caused by Early-Life Stress in Mice: A Behavioral, Histopathological, and Molecular Study.Molecular neurobiology · 2026Article
- Dissecting PANoptosis in the Nervous System: A Unified Cell-Death Mechanism Driving Neuroimmune Activation and Chronic Neuroinflammation.Molecular neurobiology · 2026Review
- A zinc-coordinated cascade-responsive therapeutic nanoassembly for remodeling the pathological microenvironment and restoring mitochondrial homeostasis in spinal cord injury.Journal of nanobiotechnology · 2026Article
- AMPK-NLRP3 Inflammasome Crosstalk: Structural Insights, Molecular Mechanisms, and Therapeutic Implications for Inflammation and Neuroinflammation.Molecular neurobiology · 2026Review
- A Age Related Vascular Senescence: Mystery of Blood-brain Barrier Dysfunction in Neurodegeneration.Molecular neurobiology · 2026Review
- Mitochondrial-Inflammatory Axis Dysregulation Triggers Disulfidptosis and the Multifaceted Protective Mechanism of Bisphenol A Following Spinal Cord Injury.Molecular neurobiology · 2026Article
- Otilonium bromide ameliorates paclitaxel-induced peripheral neuropathy by targeting phosphatase PPM1A.Journal of neuroinflammation · 2026Article
- SGK1 inhibition supports neuroprotection in spinal cord injury by suppressing oxidative stress and AIM2 activation via FoxO1 mediated mitophagy.Journal of neuroinflammation · 2026Article
- Current status and future prospects of functionalized mesenchymal stem cells for the treatment of spinal cord injury.Journal of orthopaedic translation · 2026Review
- Reprogramming the Inflammatory Response to Promote Neural Stem Cell Function After Spinal Cord Injury.Molecular neurobiology · 2026Review
- Unraveling the mechanism of tripterygium glycosides tablets-induced liver injury and the protective role of total glucosides of peony from immune-metabolic dysregulation to multi-cellular cascade.Chinese medicine · 2026Article
- NOX1/4 drives hepatic iron and lipid dysregulation, redox imbalance, and inflammation in ethanol-fed mice.Scientific reports · 2026Article
- Glaucocalyxin A Promotes Spinal Cord Repair By Nrf2/HO-1 Pathway Activation to Suppress AIM2 Inflammasome Formation.Molecular neurobiology · 2026Article
- Esculin Alleviated NLRP3 Inflammasome Activation by Inducing PINK1/Parkin-Mediated Mitophagy in Cerebral Ischemia-Reperfusion Injury.Molecular neurobiology · 2026Article
- Melatonin Alleviates Cerebral Ischemia/Reperfusion Injury by Mitigating AIM2-Mediated PANoptosis in Ischemic Penumbra.Molecular neurobiology · 2026Article
Corrections and comments
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Authors and funding
10 authors.
Funding
Abstract
Mitochondrial oxidative stress and the absent in melanoma 2 (AIM2) inflammasome play crucial roles in the regulation of secondary injury in patients with spinal cord injury (SCI). AIM2 responds to oxidative stress-mediated DNA damage, and this response leads to neuroinflammation. Salt-inducible kinase 2 (SIK2) is an AMPK-related protein kinase that plays a role in modulating cell metabolism and homeostasis. SIK2 and AIM2 are key molecules involved in metabolic regulation and the innate immune response, respectively. There is a potential association between SIK2 and AIM2 in terms of the cellular stress response, DNA damage repair and inflammatory signal transduction. However, the detailed role and mechanisms remain to be fully elucidated in the context of SCI. The present study revealed that SIK2 and AIM2 increase the number of microglia after SCI. Moreover, pharmacological inhibition of SIK2 or genetic deletion of AIM2 improves functional recovery. In addition, the SIK2 inhibitor ARN-3236, which alleviates the neuroinflammatory response, attenuates mitochondrial dysfunction and represses AIM2 activation in microglia. Mechanistically, SIK2 inhibition reduces Drp1-dependent mitochondrial fission through the CRTC1/CREB pathway, thereby decreasing mitochondrial DNA (mtDNA) leakage and AIM2 inflammasome activation, which inhibits the release of pyroptosis-related proteins and proinflammatory cytokines, ultimately mitigating neuroinflammation after SCI. Furthermore, SIK2-mediated neuroinflammation and functional recovery are related to AIM2. Thus, modulating microglial function through inhibition of SIK2 may be a viable therapeutic strategy for promoting functional recovery after SCI.
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