ArticleMolecular neurodegeneration2020
Promoting tau secretion and propagation by hyperactive p300/CBP via autophagy-lysosomal pathway in tauopathy.
Article in Molecular neurodegeneration, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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72 citing papers in PubMed, 104 citations in OpenAlex.
- Peptide-mediated inhibition of aberrant chaperone-mediated autophagy in pericytes prevents glioblastoma progression through MAPT/tau secretion.Autophagy · 2026Article
- Advances in Alzheimer's disease: mechanistic insights and therapeutic targets.Science China. Life sciences · 2026Review
- A non-canonical androgen signaling pathway drives microglial activation and tau pathology in females.Research square · 2026Article
- Recent advances in Alzheimer's disease: From molecular mechanisms to therapeutic strategies.Cell · 2026Review
- Sex-specific effects of acetylation on tauopathy in aging htau mice.Scientific reports · 2026Article
- Aerobic exercise facilitates p300 nuclear translocation via ADRB2-AMPKα signaling, leading to enhanced histone acetylation and mitigation of cognitive decline in APP/PS1 mice.Alzheimer's research & therapy · 2026Article
- Ketone body β-hydroxybutyrate restores neuronal Tau proteostasis via ketolysis-independent mechanism.bioRxiv : the preprint server for biology · 2026Article
- The modifier matrix: emerging roles of ubiquitin-like proteins in Alzheimer's disease.Molecular neurodegeneration advances · 2026Review
- Microbial SCFAs as epigenetic mediators: fine-tuning the gut-brain axis in neurodegenerative disorders.Current research in microbial sciences · 2026Review
- Post-translational modifications as a regulatory code for tau function in health and disease.Frontiers in dementia · 2026Review
- Acetylation modification in malignant progression and therapeutic resistance of gliomas.Frontiers in cell and developmental biology · 2026Review
- The deubiquitinase OTULIN regulates tau expression and RNA metabolism in neurons.Genomic psychiatry : advancing science from genes to society · 2025Article
- Decoding tau acetylation in Alzheimer's disease and tauopathies: from site-specific mechanisms to therapeutic horizons.BMB reports · 2025Review
- p300 inhibition delays premature cellular senescence.npj aging · 2025Article
- The many connections of UFMylation with Alzheimer's disease: a comprehensive review.Molecular neurodegeneration · 2025Review
- Broken Balance: Emerging Cross-Talk Between Proteostasis and Lipostasis in Neurodegenerative Diseases.Cells · 2025Review
- SON-dependent nuclear speckle rehabilitation alleviates proteinopathies.bioRxiv : the preprint server for biology · 2025Article
- GRAMD1B is a regulator of lipid homeostasis, autophagic flux and phosphorylated tau.Nature communications · 2025Article
- Inducers and modulators of protein aggregation in Alzheimer's disease - Critical tools for understanding the foundations of aggregate structures.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Lack of cellular prion protein causes Amyloid β accumulation, increased extracellular vesicle abundance, and changes to exosome biogenesis proteins.Molecular and cellular biochemistry · 2025Article
12 more citing papers are in PubMed but not listed here.
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14 authors at 3 institutions in 1 country.
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Abstract
backgroundThe trans-neuronal propagation of tau has been implicated in the progression of tau-mediated neurodegeneration. There is critical knowledge gap in understanding how tau is released and transmitted, and how that is dysregulated in diseases. Previously, we reported that lysine acetyltransferase p300/CBP acetylates tau and regulates its degradation and toxicity. However, whether p300/CBP is involved in regulation of tau secretion and propagation is unknown.
methodWe investigated the relationship between p300/CBP activity, the autophagy-lysosomal pathway (ALP) and tau secretion in mouse models of tauopathy and in cultured rodent and human neurons. Through a high-through-put compound screen, we identified a new p300 inhibitor that promotes autophagic flux and reduces tau secretion. Using fibril-induced tau spreading models in vitro and in vivo, we examined how p300/CBP regulates tau propagation.
resultsIncreased p300/CBP activity was associated with aberrant accumulation of ALP markers in a tau transgenic mouse model. p300/CBP hyperactivation blocked autophagic flux and increased tau secretion in neurons. Conversely, inhibiting p300/CBP promoted autophagic flux, reduced tau secretion, and reduced tau propagation in fibril-induced tau spreading models in vitro and in vivo.
conclusionsWe report that p300/CBP, a lysine acetyltransferase aberrantly activated in tauopathies, causes impairment in ALP, leading to excess tau secretion. This effect, together with increased intracellular tau accumulation, contributes to enhanced spreading of tau. Our findings suggest that inhibition of p300/CBP as a novel approach to correct ALP dysfunction and block disease progression in tauopathy.
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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.