ArticleJournal of neurochemistry2009
Proteasome-caspase-cathepsin sequence leading to tau pathology induced by prostaglandin J2 in neuronal cells.
Article in Journal of neurochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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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.
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Who cites it
36 citing papers in PubMed, 53 citations in OpenAlex.
- Targeting tau in Alzheimer's Disease: rationale, approach and challenges.Molecular neurodegeneration · 2026Review
- Differential effect of an evolving amyloid and tau pathology on brain phospholipids and bioactive lipid mediators in rat models of Alzheimer-like pathology.Journal of neuroinflammation · 2024Article
- Modulation of Cytosolic Phospholipase A2 as a Potential Therapeutic Strategy for Alzheimer's Disease.Journal of Alzheimer's disease reports · 2023Article
- The Anti-Neuron-Specific Enolase Antibody Induced Neuronal Cell Death in a Novel Fashion.Molecular neurobiology · 2020Article
- Cyclooxygenase-2 is critical for the propagation of β-amyloid protein and reducing the glycosylation of tau in Alzheimer's disease.Cellular & molecular immunology · 2019Article
- The Role of Eicosanoids in Alzheimer's Disease.International journal of environmental research and public health · 2019Review
- Pathophysiological Roles of Intracellular Proteases in Neuronal Development and Neurological Diseases.Molecular neurobiology · 2019Review
- The Use of Pigs as a Translational Model for Studying Neurodegenerative Diseases.Frontiers in physiology · 2019Review
- Calcium Ions Stimulate the Hyperphosphorylation of Tau by Activating Microsomal Prostaglandin E Synthase 1.Frontiers in aging neuroscience · 2019Article
- Physiological and Pathological Roles of 15-Deoxy-ΔMolecular neurobiology · 2018Review
- X-linked inhibitor of apoptosis protein (XIAP) is a client of heat shock protein 70 (Hsp70) and a biomarker of its inhibition.The Journal of biological chemistry · 2018Article
- Prostaglandin J2 promotes O-GlcNAcylation raising APP processing by α- and β-secretases: relevance to Alzheimer's disease.Neurobiology of aging · 2018Article
- COX-2 metabolic products, the prostaglandin IOncotarget · 2017Article
- Modifications of tau protein after cerebral ischemia and reperfusion in rats are similar to those occurring in Alzheimer's disease - Hyperphosphorylation and cleavage of 4- and 3-repeat tau.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2017Article
- Neurotoxic mechanisms by which the USP14 inhibitor IU1 depletes ubiquitinated proteins and Tau in rat cerebral cortical neurons: Relevance to Alzheimer's disease.Biochimica et biophysica acta. Molecular basis of disease · 2017Article
- Mass Spectrometry Analysis of Lysine Posttranslational Modifications of Tau Protein from Alzheimer's Disease Brain.Methods in molecular biology (Clifton, N.J.) · 2017Article
- Article
- Potential Long-Term Consequences of Concussive and Subconcussive Injury.Physical medicine and rehabilitation clinics of North America · 2016Review
- The Human Tau Interactome: Binding to the Ribonucleoproteome, and Impaired Binding of the Proline-to-Leucine Mutant at Position 301 (P301L) to Chaperones and the Proteasome.Molecular & cellular proteomics : MCP · 2015Article
- Emerging roles of sumoylation in the regulation of actin, microtubules, intermediate filaments, and septins.Cytoskeleton (Hoboken, N.J.) · 2015Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Neurofibrillary tangles (NFT) are a hallmark of Alzheimer's disease. The major neurofibrillary tangle component is tau that is truncated at Asp421 (Deltatau), hyperphosphorylated and aggregates into insoluble paired helical filaments. Alzheimer's disease brains also exhibit signs of inflammation manifested by activated astrocytes and microglia, which produce cytotoxic agents among them prostaglandins. We show that prostaglandin (PG) J2, an endogenous product of inflammation, induces caspase-mediated cleavage of tau, generating Deltatau, an aggregation prone form known to seed tau aggregation prior to neurofibrillary tangle formation. The initial event observed upon PGJ2-treatment of human neuroblastoma SK-N-SH cells was the build-up of ubiquitinated (Ub) proteins indicating an early disruption of the ubiquitin-proteasome pathway. Apoptosis kicked in later, manifested by caspase activation and caspase-mediated cleavage of tau at Asp421 and poly (ADP-ribose) polymerase. Furthermore, cathepsin inhibition stabilized Deltatau suggesting its lysosomal clearance. Upon PGJ2-treatment tau accumulated in a large perinuclear aggregate. In rat E18 cortical neuronal cultures PGJ2-treatment also generated Deltatau detected in dystrophic neurites. Levels of Deltatau were diminished by caspase 3 knockdown using siRNA. PGD2, the precursor of PGJ2, produced some Deltatau. PGE2 generated none. Our data suggest a potential sequence of events triggered by the neurotoxic product of inflammation PGJ2 leading to tau pathology. The accumulation of Ub proteins is an early response. If cells fail to overcome the toxic effects induced by PGJ2, including accumulation of Ub proteins, apoptosis kicks in triggering caspase activation and tau cleavage, the clearance of which by cathepsins could be compromised culminating in tau pathology. Our studies are the first to provide a mechanistic link between inflammation and tau pathology.
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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.