ArticleNature medicine2016
Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling.
Article in Nature medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 257 papers, 2 of them syntheses that pooled it.
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.
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Who cites it
257 citing papers in PubMed, 2 syntheses or guidelines pooled it, 439 citations in OpenAlex.
- The proteasome as a druggable target with multiple therapeutic potentialities: Cutting and non-cutting edges.Pharmacology & therapeutics · 2020Pooled it
- The Heart of the Alzheimer's: A Mindful View of Heart Disease.Frontiers in physiology · 2020Pooled it
- Repurposing Anticancer Drugs in Parkinson's Treatment: Molecular Pathways Driving Neuroprotection and Therapeutic Advancement.Molecular neurobiology · 2026Review
- Stimulating proteasomal degradation in human proteinopathies.The FEBS journal · 2026Review
- Proteomic comparison of hippocampal neurofibrillary tangles in PART, intermediate Alzheimer's disease and advanced Alzheimer's disease.Acta neuropathologica · 2026Article
- Epigenetic aging in Alzheimer's disease: Relation to proteome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Cholesterol at the Center of Alzheimer's Disease: A Unifying Hypothesis on the Pathogenic Mechanism.Molecules (Basel, Switzerland) · 2026Review
- Proteasome Dysfunction and Aggregation-Prone Proteins in Neurodegenerative Diseases: From Mechanisms to Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Emerging perspectives in proteostasis: bridging mechanisms and therapeutics for human diseases.Signal transduction and targeted therapy · 2026Review
- Spatial Single-Cell Proteomics Reveals Molecular Trajectories Of Tangle-Bearing Neurons In Alzheimer's Disease.bioRxiv : the preprint server for biology · 2026Article
- Neurons with granulovacuolar degeneration bodies are resilient to tau-induced protein synthesis impairment.Science advances · 2026Article
- Targeting tau in Alzheimer's Disease: rationale, approach and challenges.Molecular neurodegeneration · 2026Review
- Proteomic remodelling of the neurofibrillary tangle from "PART" to advanced Alzheimer's disease.Research square · 2026Article
- Reduction of RAD23A extends lifespan and mitigates pathology in a mouse model of TDP-43 proteinopathy.Nature communications · 2026Article
- Dystonia: Insights into Mechanisms and Novel Therapeutics.Current neurology and neuroscience reports · 2026Review
- Association between Alzheimer's disease and MHC-I antigen processing and presentation pathway: a narrative review.Frontiers in immunology · 2026Review
- Sleep and stress as modifiable drivers of Alzheimer's disease.NPJ dementia · 2026Review
- Early proteasome downregulation and dysfunction drive proteostasis failure in Alzheimer's disease.Brain : a journal of neurology · 2025Article
- The Ubiquitin-Proteasome System in Brain Disorders: Pathogenic Pathways, Post-Translational Tweaks, and Therapeutic Frontiers.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2025Review
- Current Understanding of Protein Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
197 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
The ubiquitin proteasome system (UPS) degrades misfolded proteins including those implicated in neurodegenerative diseases. We investigated the effects of tau accumulation on proteasome function in a mouse model of tauopathy and in a cross to a UPS reporter mouse (line Ub-G76V-GFP). Accumulation of insoluble tau was associated with a decrease in the peptidase activity of brain 26S proteasomes, higher levels of ubiquitinated proteins and undegraded Ub-G76V-GFP. 26S proteasomes from mice with tauopathy were physically associated with tau and were less active in hydrolyzing ubiquitinated proteins, small peptides and ATP. 26S proteasomes from normal mice incubated with recombinant oligomers or fibrils also showed lower hydrolyzing capacity in the same assays, implicating tau as a proteotoxin. Administration of an agent that activates cAMP-protein kinase A (PKA) signaling led to attenuation of proteasome dysfunction, probably through proteasome subunit phosphorylation. In vivo, this led to lower levels of aggregated tau and improvements in cognitive performance.
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What OpenQuestion holds
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.