ArticleJournal of Alzheimer's disease : JAD2017
Pazopanib Reduces Phosphorylated Tau Levels and Alters Astrocytes in a Mouse Model of Tauopathy.
Article in Journal of Alzheimer's disease : JAD, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Potential repurposing of lapatinib and pazopanib as neuroprotective agents in a rat model of Huntington's disease.Inflammopharmacology · 2025Article
- Experimental and clinical tests of FDA-approved kinase inhibitors for the treatment of neurological disorders (update 2024).Exploration of drug science · 2025Article
- Analysis of neuroglia and immune cells in the tumor microenvironment of breast cancer brain metastasis.Cancer biology & therapy · 2024Review
- c-KIT inhibitors reduce pathology and improve behavior in the Tg(SwDI) model of Alzheimer's disease.Life science alliance · 2024Article
- Dementia incidence varied by anticancer drugs and molecular targeted therapy in a population-based cohort study.Scientific reports · 2024Article
- Tyrosine kinases: multifaceted receptors at the intersection of several neurodegenerative disease-associated processes.Frontiers in dementia · 2024Review
- FDA-Approved Kinase Inhibitors in Preclinical and Clinical Trials for Neurological Disorders.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Therapeutic strategies for tauopathies and drug repurposing as a potential approach.Biochemical pharmacology · 2022Review
- Therapeutic Targeting of Repurposed Anticancer Drugs in Alzheimer's Disease: Using the Multiomics Approach.ACS omega · 2021Article
- Increased levels of Stress-inducible phosphoprotein-1 accelerates amyloid-β deposition in a mouse model of Alzheimer's disease.Acta neuropathologica communications · 2020Article
- Don't forget astrocytes when targeting Alzheimer's disease.British journal of pharmacology · 2019Review
- Multikinase Abl/DDR/Src Inhibition Produces Optimal Effects for Tyrosine Kinase Inhibition in Neurodegeneration.Drugs in R&D · 2019Article
- Histone Deacetylase Inhibitor Alleviates the Neurodegenerative Phenotypes and Histone Dysregulation in Presenilins-Deficient Mice.Frontiers in aging neuroscience · 2018Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Hyperphosphorylation and aggregation of tau protein is a critical factor in many neurodegenerative diseases. These diseases are increasing in prevalence, and there are currently no cures. Previous work from our group and others has shown that tyrosine kinase inhibitors (TKIs) can stimulate autophagy, decrease pathological proteins, and improve symptoms in models of neurodegeneration. Here we examined the role of pazopanib in mouse models that express either human mutant P301L tau (TauP301L) or triple mutant amyloid precursor protein (3x-AβPP). The TauP301L mouse expresses P301L tau under the control of a prion promoter in both neurons and astrocytes, reminiscent of some human tauopathies. Pazopanib crosses the blood-brain barrier with no detectable peripheral off-side effects, and decreases p-tau in TauP301L mice. Pazopanib reaches a brain concentration sufficient for inhibition of several tyrosine kinases, including vascular endothelial growth factor receptors (VEGFRs). Further, pazopanib does not affect microglia but reduces astrocyte levels toward nontransgenic controls in TauP301L mice. Pazopanib does not alter amyloid beta levels or astrocytes in 3x-AβPP mice but modulates a number of inflammatory markers (IP-10, MIP-1α, MIP-1β, and RANTES). These data suggest that pazopanib may be involved in p-tau clearance and modulation of astrocytic activity in models of tauopathies.
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Registered trials
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