ArticleCNS neuroscience & therapeutics2023
Degradation of NLRP3 by p62-dependent-autophagy improves cognitive function in Alzheimer's disease by maintaining the phagocytic function of microglia.
Article in CNS neuroscience & therapeutics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- Cell Death in Neurodegenerative Diseases: Molecular Mechanisms and Therapeutic Targets.MedComm · 2026Review
- Risk Factors for Cardiovascular Disease: Epidemiology, Screening, Prevention, and Therapeutic Interventions.MedComm · 2026Review
- The Glial Autophagy-Lysosomal-Inflammation Axis in Alzheimer's Disease: a Unifying Mechanistic Framework.Molecular neurobiology · 2026Review
- The roles of microglia and astrocytes in inflammasomes and neurological disorders.Neural regeneration research · 2026Article
- [Role of programmed cell death in platinum resistance in ovarian cancer].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- CSF microtubule-associated protein 1 light chain 3A and 3B levels are associated with tau pathology and Alzheimer's disease risk through amyloid deposition and microglial signaling.Journal of neuroinflammation · 2026Article
- ARC-18 Alleviates Alzheimer-like Pathology and Cognitive Deficits via AdipoR1-Mediated Activation of Autophagy and Modulation of APP Processing.Molecular neurobiology · 2026Article
- Microglia TFEB activation attenuates Alzheimer's disease pathology by enhancing autophagy-lysosomal function.Journal of neuroinflammation · 2026Article
- β-Asarone Attenuates Neuroinflammation of Alzheimer's Disease by Activating Autophagy and Suppressing NLRP3 Inflammasome Assembly.CNS neuroscience & therapeutics · 2026Article
- Piezo1-Targeted Magnetoacoustic Nanobubbles Rescue Alzheimer's Pathology by Electromechanical Neuromodulation and Amyloid-β Clearance.ACS nano · 2026Article
- Targeting microglial inflammation in Parkinson's disease: irisin activates PAFAH1B1-RAGE ubiquitination and TFEB-dependent autophagy to alleviate neurodegeneration.Communications biology · 2026Article
- Organelle stress in NLRP3 inflammasome: a central mediator of neurodegenerative diseases.Molecular neurodegeneration · 2026Review
- Protective effect of baicalein fromFrontiers in aging neuroscience · 2026Article
- Cross-talk among novel programmed cell death pathways: a decisive network in renal ischemia-reperfusion injury.Frontiers in immunology · 2026Review
- Hotspots Evolution and Cutting-Edge Trends: A Bibliometric Analysis of Autophagy in Myocardial Infarction Studies From 2007 to 2025.Cardiovascular therapeutics · 2026Review
- The APOE4-estrogen-microglia axis in perimenopausal cognitive changes: mechanisms and therapeutic implications.Frontiers in immunology · 2026Review
- The connection between autophagy and Alzheimer's disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2025Review
- Reactive Oxygen Species Across Death Pathways: Gatekeepers of Apoptosis, Ferroptosis, Pyroptosis, Paraptosis, and Beyond.International journal of molecular sciences · 2025Review
- Dexketoprofen enhances NLRP3 activation via ATPase activity after canonical stimuli.Inflammopharmacology · 2025Article
- Association Analysis Between Ischemic Stroke Risk Single Nucleotide Polymorphisms and Alzheimer's Disease.Bioengineering (Basel, Switzerland) · 2025Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
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Abstract
backgroundActivation of the NLRP3 inflammasome promotes microglia to secrete inflammatory cytokines and induce pyroptosis, leading to impaired phagocytic and clearance functions of microglia in Alzheimer's disease (AD). This study found that the autophagy-associated protein p62 interacts with NLRP3, which is the rate-limiting protein of the NLRP3 inflammasome. Thus, we aimed to prove that the degradation of NLRP3 occurs through the autophagy-lysosome pathway (ALP) and also demonstrate its effects on the function of microglia and pathological changes in AD.
methodsThe 5XFAD/NLRP3-KO mouse model was established to study the effect of NLRP3 reduction on AD. Behavioral experiments were conducted to assess the cognitive function of the mice. In addition, immunohistochemistry was used to evaluate the deposition of Aβ plaques and morphological changes in microglia. BV2 cells treated with lipopolysaccharide (LPS) followed by Aβ1-42 oligomers were used as in vitro AD inflammation models and transfected with lentivirus to regulate the expression of the target protein. The pro-inflammatory status and function of BV2 cells were detected by flow cytometry and immunofluorescence (IF). Co-immunoprecipitation, mass spectrometry, IF, Western blot (WB), quantitative real-time PCR, and RNA-seq analysis were used to elucidate the mechanisms of molecular regulation.
resultsCognitive function was improved in the 5XFAD/NLRP3-KO mouse model by reducing the pro-inflammatory response of microglia and maintaining the phagocytic and clearance function of microglia to the deposited Aβ plaque. The pro-inflammatory function and pyroptosis of microglia were regulated by NLRP3 expression. Ubiquitinated NLRP3 can be recognized by p62 and degraded by ALP, slowing down the proinflammatory function and pyroptosis of microglia. The expression of autophagy pathway-related proteins such as LC3B/A, p62 was increased in the AD model in vitro.
conclusionsP62 recognizes and binds to ubiquitin-modified NLRP3. It plays a vital role in regulating the inflammatory response by participating in ALP-associated NLRP3 protein degradation, which improves cognitive function in AD by reducing the pro-inflammatory status and pyroptosis of microglia, thus maintaining its phagocytic function.
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