ArticleJournal of neuroinflammation2016
LRP1 modulates the microglial immune response via regulation of JNK and NF-κB signaling pathways.
Article in Journal of neuroinflammation, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 86 papers, 1 of them a synthesis that pooled it.
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Who cites it
86 citing papers in PubMed, 1 synthesis or guideline pooled it, 159 citations in OpenAlex.
- Genome-wide association susceptibility loci for cluster headache support a role for inflammation in the pathophysiology.The journal of headache and pain · 2026Pooled it
- Apolipoprotein E Mimetic Peptide CN-105 and Postoperative Delirium in Older Patients: The Phase 2 MARBLE Randomized Clinical Trial.JAMA network open · 2026Trial
- NF-κB across the Alzheimer disease spectrum: Context-dependent protective and pathogenic roles.IBRO neuroscience reports · 2026Review
- Review
- Restores Aβ Clearance by Overcoming PCSK9-LRP1 Dysregulation and TRIB3-Mediated Autophagy Blockade in Alzheimer's Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Isaridin E Attenuates Ischemic Brain Injury in Mice by Concurrently Reducing Platelet Hyperactivity and Microglial Neuroinflammation Associated with LRP1.Marine drugs · 2026Article
- PQBP1-dependent alternative RNA splicing underlies high calorie diet-induced cognitive impairment.Molecular psychiatry · 2026Article
- An ApoE-Associated Low-Inflammatory Microglial State Emerges After Inflammatory Challenge in Alzheimer's Disease Mice.Neuroscience bulletin · 2026Article
- Review
- Body weight-supported treadmill training enhances motor recovery and ameliorates neuron injury through the MDK/LRP-1 signaling pathway in T10 incomplete spinal cord-injured rats.Neurochemical research · 2026Article
- LRP1 Activation Promotes Metabolic Reprogramming and Mrc1 Expression to Attenuate LPS-Induced Cognitive Deficits: An Integrated Omics Analysis.CNS neuroscience & therapeutics · 2026Article
- Single-nucleus brain transcriptomics reveals microglia dysfunction in multiple system atrophy.Nature communications · 2026Article
- Midkine Overexpression Promotes Functional Recovery After Spinal Cord Injury by Enhancing Microglial Efferocytosis Via LRP-1.CNS neuroscience & therapeutics · 2026Article
- Entrectinib attenuates LPS-induced neuroinflammation by inhibiting JNK, p38, and AKT pathways and ameliorates cognitive impairment.Archives of pharmacal research · 2026Article
- Emerging Potential of Ras-proximate-1 (Rap1) in Mediating Neurodegenerative Diseases.Current neuropharmacology · 2026Review
- Midkine-Mediated Microglia Activation after Renal Injury Promotes Cognitive Impairment Following Ischemic Renal Injury.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Role and Therapeutic Potential of the cGAS-STING Signaling Pathway in Alzheimer's Disease.Brain and behavior · 2025Review
- "Rewiring brain immunity: targeting microglial metabolism for neuroprotection in neurodegenerative disorders".Metabolic brain disease · 2025Review
- Inhibition of Acyl-CoenzymeA: Cholesterol Acyltransferase 1 promotes shedding of soluble triggering receptor on myeloid cells 2 (TREM2) and low-density lipoprotein receptor 1 (LRP1)-dependent phagocytosis of amyloid beta protein in microglia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Microglial Dysfunction and Amyloid-Beta Pathology in Alzheimer's Disease and HIV-Associated Neurocognitive Disorders.International journal of molecular sciences · 2025Review
26 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundNeuroinflammation is characterized by microglial activation and the increased levels of cytokines and chemokines in the central nervous system (CNS). Recent evidence has implicated both beneficial and toxic roles of microglia when over-activated upon nerve injury or in neurodegenerative diseases, including Alzheimer's disease (AD). The low-density lipoprotein receptor-related protein 1 (LRP1) is a major receptor for apolipoprotein E (apoE) and amyloid-β (Aβ), which play critical roles in AD pathogenesis. LRP1 regulates inflammatory responses in peripheral tissues by modulating the release of inflammatory cytokines and phagocytosis. However, the roles of LRP1 in brain innate immunity and neuroinflammation remain unclear.
methodsIn this study, we determined whether LRP1 modulates microglial activation by knocking down Lrp1 in mouse primary microglia. LRP1-related functions in microglia were also assessed in the presence of LRP1 antagonist, the receptor-associated protein (RAP). The effects on the production of inflammatory cytokines were measured by quantitative real-time PCR (qRT-PCR) and enzyme-linked immunosorbent assay (ELISA). Potential involvement of specific signaling pathways in LRP1-regulated functions including mitogen-activated protein kinases (MAPKs) and nuclear factor-κB (NF-κB) were assessed using specific inhibitors.
resultsWe found that knocking down of Lrp1 in mouse primary microglia led to the activation of both c-Jun N-terminal kinase (JNK) and NF-κB pathways with corresponding enhanced sensitivity to lipopolysaccharide (LPS) in the production of pro-inflammatory cytokines. Similar effects were observed when microglia were treated with LRP1 antagonist RAP. In addition, treatment with pro-inflammatory stimuli suppressed Lrp1 expression in microglia. Interestingly, NF-κB inhibitor not only suppressed the production of cytokines induced by the knockdown of Lrp1 but also restored the down-regulated expression of Lrp1 by LPS.
conclusionsOur study uncovers that LRP1 suppresses microglial activation by modulating JNK and NF-κB signaling pathways. Given that dysregulation of LRP1 has been associated with AD pathogenesis, our work reveals a critical regulatory mechanism of microglial activation by LRP1 that could be associated with other AD-related pathways thus further nominating LRP1 as a potential disease-modifying target for the treatment of AD.
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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.