ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2000
Inflammatory mechanisms in Alzheimer's disease: inhibition of beta-amyloid-stimulated proinflammatory responses and neurotoxicity by PPARgamma agonists.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 212 papers, 3 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
212 citing papers in PubMed, 3 syntheses or guidelines pooled it, 565 citations in OpenAlex.
- Alzheimer's Disease and Inflammation Research: A Systematic Bibliometric Review and Network Visualization of the Published Literature Between 2000 and 2023.Recent advances in inflammation & allergy drug discovery · 2026Pooled it
- Therapeutic Potential for Cannabidiol on Alzheimer's Disease-Related Neuroinflammation: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2025Pooled it
- Laminin as a Biomarker of Blood-Brain Barrier Disruption under Neuroinflammation: A Systematic Review.International journal of molecular sciences · 2022Pooled it
- Assembling peptides for treating Alzheimer's disease: a supramolecular perspective.RSC advances · 2026Review
- Metabolic breakdown: Linking insulin resistance and mitochondrial dysfunction to neurodegeneration in Alzheimer's disease.Neural regeneration research · 2026Article
- Capillary-Associated Microglia in Neurovascular Coupling: Localization, Mechanisms, and Disease Implications.Journal of neuroinflammation · 2026Review
- Unraveling the Function of PPARα in Neurodegenerative Disorders: A Potential Pathway to Novel Therapies.Biomedicines · 2025Review
- Neuroprotective role of rice bran extract and its constituents in a neuroinflammatory mouse model.BMC complementary medicine and therapies · 2025Article
- From defense to disease: IFITM3 in immunity and Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Antiageing strategy for neurodegenerative diseases: from mechanisms to clinical advances.Signal transduction and targeted therapy · 2025Review
- Ketogenic diet, adenosine, and dopamine in addiction and psychiatry.Frontiers in nutrition · 2025Review
- Sodium Thiosulfate: An Innovative Multi-Target Repurposed Treatment Strategy for Late-Onset Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Insulin Resistance, a Risk Factor for Alzheimer's Disease: Pathological Mechanisms and a New Proposal for a Preventive Therapeutic Approach.Biomedicines · 2024Review
- Loss of Direct Vascular Contact to Astrocytes in the Hippocampus as an Initial Event in Alzheimer's Disease. Evidence from Patients, In Vivo and In Vitro Experimental Models.Molecular neurobiology · 2024Article
- Strategies for modeling aging and age-related diseases.npj aging · 2024Review
- PPARs in Clinical Experimental Medicine after 35 Years of Worldwide Scientific Investigations and Medical Experiments.Biomolecules · 2024Review
- Current View on PPAR-α and Its Relation to Neurosteroids in Alzheimer's Disease and Other Neuropsychiatric Disorders: Promising Targets in a Therapeutic Strategy.International journal of molecular sciences · 2024Review
- Glial reactivity in a mouse model of beta-amyloid deposition assessed by PET imaging of P2X7 receptor and TSPO using [EJNMMI research · 2024Article
- Nanotechnology for microglial targeting and inhibition of neuroinflammation underlying Alzheimer's pathology.Translational neurodegeneration · 2024Article
- Amyloid β-based therapy for Alzheimer's disease: challenges, successes and future.Signal transduction and targeted therapy · 2023Review
152 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is characterized by the extracellular deposition of beta-amyloid fibrils within the brain and the subsequent association and phenotypic activation of microglial cells associated with the amyloid plaque. The activated microglia mount a complex local proinflammatory response with the secretion of a diverse range of inflammatory products. Nonsteroidal anti-inflammatory drugs (NSAIDs) are efficacious in reducing the incidence and risk of AD and significantly delaying disease progression. A recently appreciated target of NSAIDs is the ligand-activated nuclear receptor peroxisome proliferator-activated receptor gamma (PPARgamma). PPARgamma is a DNA-binding transcription factor whose transcriptional regulatory actions are activated after agonist binding. We report that NSAIDs, drugs of the thiazolidinedione class, and the natural ligand prostaglandin J2 act as agonists for PPARgamma and inhibit the beta-amyloid-stimulated secretion of proinflammatory products by microglia and monocytes responsible for neurotoxicity and astrocyte activation. The activation of PPARgamma also arrested the differentiation of monocytes into activated macrophages. PPARgamma agonists were shown to inhibit the beta-amyloid-stimulated expression of the cytokine genes interleukin-6 and tumor necrosis factor alpha. Furthermore, PPARgamma agonists inhibited the expression of cyclooxygenase-2. These data provide direct evidence that PPARgamma plays a critical role in regulating the inflammatory responses of microglia and monocytes to beta-amyloid. We argue that the efficacy of NSAIDs in the treatment of AD may be a consequence of their actions on PPARgamma rather than on their canonical targets the cyclooxygenases. Importantly, the efficacy of these agents in inhibiting a broad range of inflammatory responses suggests PPARgamma agonists may provide a novel therapeutic approach to AD.
Indexed as
Identifiers
10632585PMC6772401W1896225205What OpenQuestion holds
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.