ArticleThe journal of physiological sciences : JPS2020
Tolfenamic acid inhibits GSK-3β and PP2A mediated tau hyperphosphorylation in Alzheimer's disease models.
Article in The journal of physiological sciences : JPS, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers, 1 of them a synthesis that pooled it.
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Who cites it
25 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- C/EBPβ: A transcription factor associated with the irreversible progression of Alzheimer's disease.CNS neuroscience & therapeutics · 2024Pooled it
- Neuroprotective Mechanisms of Ficus deltoidea in an Alzheimer's Disease-Like Rat Model: Targeting Tau Hyperphosphorylation Through Glycogen Synthase Kinase-3 Beta and Protein Phosphatase 2A Regulation.Neurochemical research · 2026Article
- Targeting of the PI3 K/AKT/GSK3β Pathway in Parkinson's Disease: A Therapeutic Blueprint.Molecular neurobiology · 2025Review
- Pleiotropic regulatory mechanisms and targeted therapeutic prospects of Galectin-3 in aging-related diseases.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Alkaloids from Caliphruria subedentata (Amaryllidaceae) as Regulators of AChE, BuChE, NMDA and GSK3 Activity: An In Vitro and In Silico Approach for Mimicking Alzheimer´s Disease.Neurochemical research · 2025Article
- Natural products against tau hyperphosphorylation-induced aggregates: Potential therapies for Alzheimer's disease.Archiv der Pharmazie · 2025Review
- A biomimetic upconversion nanoreactors for near-infrared driven HBioactive materials · 2024Article
- Therapeutic Potential Effect of Glycogen Synthase Kinase 3 Beta (GSK-3β) Inhibitors in Parkinson Disease: Exploring an Overlooked Avenue.Molecular neurobiology · 2024Review
- Article
- Nootropic effect of Indian Royal Jelly against okadaic acid induced rat model of Alzheimer's disease: Inhibition of neuroinflammation and acetylcholineesterase.Journal of traditional and complementary medicine · 2024Article
- Exploring the role of COX-2 in Alzheimer's disease: Potential therapeutic implications of COX-2 inhibitors.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2023Review
- Mitochondrial dynamics in neurological diseases: a narrative review.Annals of translational medicine · 2023Review
- Alternative Pharmacological Strategies for the Treatment of Alzheimer's Disease: Focus on Neuromodulator Function.Biomedicines · 2022Review
- Combination of indirect revascularization and endothelial progenitor cell transplantation improved cerebral perfusion and ameliorated tauopathy in a rat model of bilateral ICA ligation.Stem cell research & therapy · 2022Article
- Inhibition of NLRP1-Dependent Pyroptosis Prevents Glycogen Synthase Kinase-3β Overactivation-Induced Hyperphosphorylated Tau in Rats.Neurotoxicity research · 2022Article
- miR-212-3p attenuates neuroinflammation of rats with Alzheimer's disease via regulating the SP1/BACE1/NLRP3/Caspase-1 signaling pathway.Bosnian journal of basic medical sciences · 2022Article
- Cryptotanshinone Attenuates Amyloid-βMolecular neurobiology · 2022Article
- Targeting protein phosphatases for the treatment of inflammation-related diseases: From signaling to therapy.Signal transduction and targeted therapy · 2022Review
- Mitochondrial dynamics in the neonatal brain - a potential target following injury?Bioscience reports · 2022Review
- Evolving concepts in progressive supranuclear palsy and other 4-repeat tauopathies.Nature reviews. Neurology · 2021Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Tolfenamic acid, a nonsteroidal anti-inflammatory drug, alleviated learning and memory deficits and decreased the expression of specificity protein 1 (SP1)-mediated cyclin-dependent kinase-5 (CDK5), a major protein kinase that regulates hyperphosphorylated tau, in Alzheimer's disease (AD) transgenic mice. However, whether tolfenamic acid can regulate the major tau protein kinase, glycogen synthase kinase-3β (GSK-3β), or tau protein phosphatase, protein phosphatase 2A (PP2A), further inhibiting hyperphosphorylation of tau, remains unknown. To this end, tolfenamic acid was administered i.p. in a GSK-3β overactivation postnatal rat model and orally in mice after intracerebroventricular (ICV) injection of okadaic acid (OA) to develop a PP2A inhibition model. We used four behavioural experiments to evaluate memory function in ICV-OA mice. In this study, tolfenamic acid attenuated memory dysfunction. Tolfenamic acid decreased the expression of hyperphosphorylated tau in the brain by inhibiting GSK-3β activity, decreasing phosphorylated PP2A (Tyr307), and enhancing PP2A activity. Tolfenamic acid also increased wortmannin (WT) and GF-109203X (GFX) induced phosphorylation of GSK-3β (Ser9) and prevented OA-induced downregulation of PP2A activity in PC12 cells. Altogether, these results show that tolfenamic acid not only decreased SP1/CDK5-mediated tau phosphorylation, but also inhibited GSK-3β and PP2A-mediated tau hyperphosphorylation in AD models.
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