ArticleActa pharmacologica Sinica2023
Pazopanib alleviates neuroinflammation and protects dopaminergic neurons in LPS-stimulated mouse model by inhibiting MEK4-JNK-AP-1 pathway.
Article in Acta pharmacologica Sinica, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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17 citing papers in PubMed, 30 citations in OpenAlex.
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- Unraveling Parkinson's disease: The mystery of mitochondria and the role of aging.Genes & diseases · 2026Review
- Potential repurposing of lapatinib and pazopanib as neuroprotective agents in a rat model of Huntington's disease.Inflammopharmacology · 2025Article
- Targeting JNK1/2 and P38 Mitogen-Activated Protein Kinases With Pazopanib Mitigates Bleomycin-Induced Lung Fibrosis.Archiv der Pharmazie · 2025Article
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- Alpha‑Asarone Ameliorates Neuronal Injury After Ischemic Stroke and Hemorrhagic Transformation by Attenuating Blood-Brain Barrier Destruction, Promoting Neurogenesis, and Inhibiting Neuroinflammation.Molecular neurobiology · 2025Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
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- ABBV-744 alleviates LPS-induced neuroinflammation via regulation of BATF2-IRF4-STAT1/3/5 axis.Acta pharmacologica Sinica · 2024Article
- Ferroptosis: a new promising target for hepatocellular carcinoma therapy.Molecular and cellular biochemistry · 2024Review
- Hypoxia Pathways in Parkinson's Disease: From Pathogenesis to Therapeutic Targets.International journal of molecular sciences · 2024Review
- BHBA attenuates endoplasmic reticulum stress-dependent neuroinflammation via the gut-brain axis in a mouse model of heat stress.CNS neuroscience & therapeutics · 2024Article
- Deficient chaperone-mediated autophagy facilitates LPS-induced microglial activation via regulation of the p300/NF-κB/NLRP3 pathway.Science advances · 2023Article
- Orientin regulates the proliferation and migration of hepatocellular carcinoma cells.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Loss of DJ-1 function contributes to Parkinson's disease pathogenesis in mice via RACK1-mediated PKC activation and MAO-B upregulation.Acta pharmacologica Sinica · 2023Article
- Exploring potential SARS-CoV-2 Mpro non-covalent inhibitors through docking, pharmacophore profile matching, molecular dynamic simulation, and MM-GBSA.Journal of molecular modeling · 2023Article
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Parkinson's disease (PD) is a progressive neurodegenerative disease characterized by the loss of dopaminergic (DA) neurons and the accumulation of Lewy bodies (LB) in the substantia nigra (SN). Evidence shows that microglia-mediated neuroinflammation plays a key role in PD pathogenesis. Using TNF-α as an indicator for microglial activation, we established a cellular model to screen compounds that could inhibit neuroinflammation. From 2471 compounds in a small molecular compound library composed of FDA-approved drugs, we found 77 candidates with a significant anti-inflammatory effect. In this study, we further characterized pazopanib, a pan-VEGF receptor tyrosine kinase inhibitor (that was approved by the FDA for the treatment of advanced renal cell carcinoma and advanced soft tissue sarcoma). We showed that pretreatment with pazopanib (1, 5, 10 μM) dose-dependently suppressed LPS-induced BV2 cell activation evidenced by inhibiting the transcription of proinflammatory factors iNOS, COX2, Il-1β, and Il-6 through the MEK4-JNK-AP-1 pathway. The conditioned medium from LPS-treated microglia caused mouse DA neuronal MES23.5 cell damage, which was greatly attenuated by pretreatment of the microglia with pazopanib. We established an LPS-stimulated mouse model by stereotactic injection of LPS into mouse substantia nigra. Administration of pazopanib (10 mg·kg
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