ArticleAging cell2022
Central role for p62/SQSTM1 in the elimination of toxic tau species in a mouse model of tauopathy.
Article in Aging cell, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
29 citing papers in PubMed, 45 citations in OpenAlex.
- The immunoproteasome in Alzheimer's disease: a dual regulator of tau pathology and microglial senescence.Inflammopharmacology · 2026Review
- Autophagy and selective autophagy receptors: Key players against Alzheimer's disease.Neural regeneration research · 2026Article
- Roles of autophagy in brain homeostasis and disease.Nature neuroscience · 2026Review
- Peripheral and Central miRNA Signatures in Alzheimer's Disease: Tissue-Specific Variability, Sex-Associated Differences, and Implications for Blood-Based Biomarkers.International journal of molecular sciences · 2026Review
- A pathogenic Tau mutation drives autophagy-lysosome dysfunction that limits Tau degradation in a model of frontotemporal dementia.Nature communications · 2026Article
- Current Understanding of Protein Aggregation in Neurodegenerative Diseases.International journal of molecular sciences · 2025Review
- Spontaneous pathology in PS19 tauopathy mice progresses via brain networks.Neurobiology of disease · 2025Article
- Mitochondria and Endoplasmic Reticulum Contact Site as a Regulator of Proteostatic Stress Responses in Neurodegenerative Diseases.BioEssays : news and reviews in molecular, cellular and developmental biology · 2025Review
- Tau degradation in Alzheimer's disease: Mechanisms and therapeutic opportunities.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Large-scale deep proteomic analysis in Alzheimer's disease brain regions across race and ethnicity.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- The Mechanistic Link Between Tau-Driven Proteotoxic Stress and Cellular Senescence in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- PLK2-mediated phosphorylation of SQSTM1 S349 promotes aggregation of polyubiquitinated proteins upon proteasomal dysfunction.Autophagy · 2024Article
- Proximity labeling reveals dynamic changes in the SQSTM1 protein network.bioRxiv : the preprint server for biology · 2024Article
- The influence of APOEActa neuropathologica · 2024Article
- Involvement of the glymphatic/meningeal lymphatic system in Alzheimer's disease: insights into proteostasis and future directions.Cellular and molecular life sciences : CMLS · 2024Review
- Precision proteoform design for 4R tau isoform selective templated aggregation.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Loss of TMEM106B exacerbates Tau pathology and neurodegeneration in PS19 mice.Acta neuropathologica · 2024Article
- BAG3 regulates the specificity of the recognition of specific MAPT species by NBR1 and SQSTM1.Autophagy · 2024Article
- Diagnostic and therapeutic targeting of pathological tau proteins in neurodegenerative disorders.FEBS open bio · 2024Review
- Research on the molecular mechanism of singularity phenomenon in neurological disorders.Biophysics and physicobiology · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
14 authors at 6 institutions in 3 countries.
Funding
Abstract
Intracellular accumulation of filamentous tau aggregates with progressive neuronal loss is a common characteristic of tauopathies. Although the neurodegenerative mechanism of tau-associated pathology remains unclear, molecular elements capable of degrading and/or sequestering neurotoxic tau species may suppress neurodegenerative progression. Here, we provide evidence that p62/SQSTM1, a ubiquitinated cargo receptor for selective autophagy, acts protectively against neuronal death and neuroinflammation provoked by abnormal tau accumulation. P301S mutant tau transgenic mice (line PS19) exhibited accumulation of neurofibrillary tangles with localization of p62 mostly in the brainstem, but neuronal loss with few neurofibrillary tangles in the hippocampus. In the hippocampus of PS19 mice, the p62 level was lower compared to the brainstem, and punctate accumulation of phosphorylated tau unaccompanied by co-localization of p62 was observed. In PS19 mice deficient in p62 (PS19/p62-KO), increased accumulation of phosphorylated tau, acceleration of neuronal loss, and exacerbation of neuroinflammation were observed in the hippocampus as compared with PS19 mice. In addition, increase of abnormal tau and neuroinflammation were observed in the brainstem of PS19/p62-KO. Immunostaining and dot-blot analysis with an antibody selectively recognizing tau dimers and higher-order oligomers revealed that oligomeric tau species in PS19/p62-KO mice were significantly accumulated as compared to PS19 mice, suggesting the requirement of p62 to eliminate disease-related oligomeric tau species. Our findings indicated that p62 exerts neuroprotection against tau pathologies by eliminating neurotoxic tau species, suggesting that the manipulative p62 and selective autophagy may provide an intrinsic therapy for the treatment of tauopathy.
Indexed as
Identifiers
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.