ArticleNature medicine2015
Critical role of acetylation in tau-mediated neurodegeneration and cognitive deficits.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03277573 (A Phase 1b, 12-Month, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Salsalate in Patients With Mild to Moderate Alzheimer's Disease), which is not on this map. Cited by 299 papers.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 1b, 12-Month, Randomized, Double-Blind, Placebo-Controlled Study of the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Preliminary Efficacy of Salsalate in Patients With Mild to Moderate Alzheimer's Disease
Who cites it
299 citing papers in PubMed, 490 citations in OpenAlex.
- Modifications of Lysine Residues 294 and 311 Within the Microtubule-Binding Region Alter Tau Aggregation and Tubulin Binding Equilibria.Angewandte Chemie (International ed. in English) · 2026Article
- SIRT1 in Neurodegenerative Diseases: Molecular Mechanisms, Disease Relevance, and Therapeutic Potential.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- Rethinking tau-targeted therapy in Alzheimer's disease: Toward a dual biomarker strategy.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- Metal Binding to Tau Protein: Physiological and Pathological Relevance.Biochemistry · 2026Review
- Tau-mediated Mechanisms in Alzheimer's Disease Pathogenesis.Molecular neurobiology · 2026Review
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Epigenetic dynamics of cellular senescence: From mechanistic insights to precision senotherapy.Chinese medical journal · 2026Review
- Multi-omics and artificial intelligence for precision drug discovery and potential clinical applications.Signal transduction and targeted therapy · 2026Review
- Biophysical assessment of the molecular mechanisms of Tau aggregation and its role in Alzheimer's disease.Protein science : a publication of the Protein Society · 2026Review
- An acetylated Tau-174 CSF biomarker discriminates between TDP-43 and tau pathology in patients with frontotemporal lobar degeneration.Nature medicine · 2026Article
- Reduced ULK1 links impaired autophagy and mitophagy to Alzheimer's disease pathology.Nature aging · 2026Article
- Unrevealing possible mechanism of Riluzole, Salsalate and Nimodipine in Alzheimer's disease: multi-target network pharmacological perspective.Inflammopharmacology · 2026Article
- Beyond microtubule regulation: the multifaceted roles of tau in neuronal function and dysfunction.Translational psychiatry · 2026Review
- Sex-specific effects of acetylation on tauopathy in aging htau mice.Scientific reports · 2026Article
- Targeting tau in Alzheimer's Disease: rationale, approach and challenges.Molecular neurodegeneration · 2026Review
- Tau in Alzheimer's disease: Shaping the future patient journey.The journal of prevention of Alzheimer's disease · 2026Review
- Drosophila wing is a high-throughput and versatile screening tool for Tau-mediated disease mechanisms and drug discovery.Disease models & mechanisms · 2026Article
- HDAC6 Inhibition Reduces Seeded Tau and α-Synuclein Pathologies in Primary Neuron Cultures and Wild-Type Mice.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Artificial Intelligence to Guide Repurposing of Drugs.Annual review of medicine · 2026Review
239 more citing papers are in PubMed but not listed here.
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Authors and funding
22 authors at 5 institutions in 1 country.
Funding
Abstract
Tauopathies, including frontotemporal dementia (FTD) and Alzheimer's disease (AD), are neurodegenerative diseases in which tau fibrils accumulate. Recent evidence supports soluble tau species as the major toxic species. How soluble tau accumulates and causes neurodegeneration remains unclear. Here we identify tau acetylation at Lys174 (K174) as an early change in AD brains and a critical determinant in tau homeostasis and toxicity in mice. The acetyl-mimicking mutant K174Q slows tau turnover and induces cognitive deficits in vivo. Acetyltransferase p300-induced tau acetylation is inhibited by salsalate and salicylate, which enhance tau turnover and reduce tau levels. In the PS19 transgenic mouse model of FTD, administration of salsalate after disease onset inhibited p300 activity, lowered levels of total tau and tau acetylated at K174, rescued tau-induced memory deficits and prevented hippocampal atrophy. The tau-lowering and protective effects of salsalate were diminished in neurons expressing K174Q tau. Targeting tau acetylation could be a new therapeutic strategy against human tauopathies.
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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.