ArticleNeuropharmacology2014
Tolfenamic acid downregulates BACE1 and protects against lead-induced upregulation of Alzheimer's disease related biomarkers.
Article in Neuropharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 45 citations in OpenAlex.
- Pharmacotherapies for the Treatment of Progressive Supranuclear Palsy: A Narrative Review.Neurology and therapy · 2024Review
- Analysis of Tolfenamic Acid using a Simple, Rapid, and Stability-indicating Validated HPLC Method.Anti-inflammatory & anti-allergy agents in medicinal chemistry · 2024Article
- A story of the potential effect of non-steroidal anti-inflammatory drugs (NSAIDs) in Parkinson's disease: beneficial or detrimental effects.Inflammopharmacology · 2023Review
- Microglia as a cellular target of diclofenac therapy in Alzheimer's disease.Therapeutic advances in neurological disorders · 2023Review
- Tolfenamic acid inhibits ROS-generating oxidase Nox1-regulated p53 activity in intrastriatal injection of malonic acid rats.The journal of physiological sciences : JPS · 2022Article
- Environmental exposures and the etiopathogenesis of Alzheimer's disease: The potential role of BACE1 as a critical neurotoxic target.Journal of biochemical and molecular toxicology · 2021Review
- Review
- Tolfenamic acid inhibits GSK-3β and PP2A mediated tau hyperphosphorylation in Alzheimer's disease models.The journal of physiological sciences : JPS · 2020Article
- Machine learning prediction of incidence of Alzheimer's disease using large-scale administrative health data.NPJ digital medicine · 2020Article
- Loss in efficacy measures of tolfenamic acid in a tau knock-out model: Relevance to Alzheimer's disease.Experimental biology and medicine (Maywood, N.J.) · 2019Article
- Article
- Prevention of Huntington's Disease-Like Behavioral Deficits in R6/1 Mouse by Tolfenamic Acid Is Associated with Decreases in Mutant Huntingtin and Oxidative Stress.Oxidative medicine and cellular longevity · 2019Article
- Tolfenamic Acid Attenuates 3-Nitropropionic Acid-Induced Biochemical Alteration in Mice.Neurochemical research · 2018Article
- Tolfenamic Acid: A Modifier of the Tau Protein and its Role in Cognition and Tauopathy.Current Alzheimer research · 2018Article
- Inflammasomes as therapeutic targets for Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2017Review
- Mithramycin A Alleviates Cognitive Deficits and Reduces Neuropathology in a Transgenic Mouse Model of Alzheimer's Disease.Neurochemical research · 2016Article
- Mitochondrial dysfunction and cell death in neurodegenerative diseases through nitroxidative stress.Brain research · 2016Review
- Tolfenamic acid reduces tau and CDK5 levels: implications for dementia and tauopathies.Journal of neurochemistry · 2015Article
- Validation of a UV Spectrometric Method for the Assay of Tolfenamic Acid in Organic Solvents.Journal of pharmaceutics · 2015Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Environmental exposure to lead (Pb) early in life results in a latent upregulation of genes and products associated with Alzheimer's disease (AD), particularly the plaque forming protein amyloid beta (Aβ). Furthermore, animals exposed to Pb as infants develop cognitive decline and memory impairments in old age. Studies from our lab demonstrated that tolfenamic acid lowers the levels of the amyloid β precursor protein (APP) and its aggregative cleavage product Aβ by inducing the degradation of the transcription factor specificity protein 1 (Sp1). These changes were accompanied by cognitive improvement in transgenic APP knock-in mice. In this study, we examined the effects of tolfenamic acid on beta site APP cleaving enzyme 1 (BACE1) which is responsible for Aβ production and tested its ability to reverse Pb-induced upregulation in the amyloidogenic pathway. Mice were administered tolfenamic acid for one month and BACE1 gene expression as well as its enzymatic activity were analyzed in the cerebral cortex. Tolfenamic acid was also tested for its ability to reverse changes in Sp1, APP and Aβ that were upregulated by Pb in vitro. Differentiated SH-SY5Y neuroblastoma cells were either left unexposed, or sequentially exposed to Pb followed by tolfenamic acid. Our results show that tolfenamic acid reduced BACE1 gene expression and enzyme activity in mice. In neuroblastoma cells, Pb upregulated Sp1, APP and Aβ, while tolfenamic acid lowered their expression. These results along with previous data from our lab provide evidence that tolfenamic acid, a drug that has been used for decades for migraine, represents a candidate which can reduce the pathology of AD and may mitigate the damage of environmental risk factors associated with this disease.
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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.