ArticleAutophagy2018
Pathological missorting of endogenous MAPT/Tau in neurons caused by failure of protein degradation systems.
Article in Autophagy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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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
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 37 citations in OpenAlex.
- Neurodevelopmental Clues to Neurodegeneration.Pediatric neurology · 2021Pooled it
- Dendritic translation and neuroproteasome-mediated degradation of endogenous tau revealed by STARFISH.Nature neuroscience · 2026Article
- Article
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- Impact and Significance of Viral Vectors for siRNA Delivery in the Treatment of Alzheimer's Disease.Current pharmaceutical biotechnology · 2026Review
- Myelin-axon interface vulnerability in Alzheimer's disease revealed by subcellular proteomics and imaging of human and mouse brain.Nature neuroscience · 2025Article
- The tau isoform 1N4R confers vulnerability of MAPT knockout human iPSC-derived neurons to amyloid beta and phosphorylated tau-induced neuronal dysfunction.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Effect of calcium ions on the aggregation of highly phosphorylated tau.Biochemistry and biophysics reports · 2024Article
- The six brain-specific TAU isoforms and their role in Alzheimer's disease and related neurodegenerative dementia syndromes.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Review
- FMRP-mediated spatial regulation of physiologic NMD targets in neuronal cells.Genome biology · 2024Review
- 5-HT4 receptor agonists treatment reduces tau pathology and behavioral deficit in the PS19 mouse model of tauopathy.Frontiers in cellular neuroscience · 2024Article
- Tau here, tau there, tau almost everywhere: Clarifying the distribution of tau in the adult CNS.Cytoskeleton (Hoboken, N.J.) · 2024Article
- Laser-Induced Axotomy of Human iPSC-Derived and Murine Primary Neurons Decreases Somatic Tau and AT8 Tau Phosphorylation: A Single-Cell Approach to Study Effects of Acute Axonal Damage.Cellular and molecular neurobiology · 2023Article
- Posttranscriptional regulation of neurofilament proteins and tau in health and disease.Brain research bulletin · 2023Review
- Microfluidic Chamber Technology to Study Missorting and Spreading of Tau Protein in Alzheimer's Disease.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Tau mRNA Metabolism in Neurodegenerative Diseases: A Tangle Journey.Biomedicines · 2022Review
- Revisiting the Role of GSK3, A Modulator of Innate Immunity, in Idiopathic Inclusion Body Myositis.Cells · 2021Review
- PAC1 receptor-mediated clearance of tau in postsynaptic compartments attenuates tau pathology in mouse brain.Science translational medicine · 2021Article
- Tau Ubiquitination in Alzheimer's Disease.Frontiers in neurology · 2021Review
- Current Evidence on the Protective Effects of Recombinant Human Erythropoietin and Its Molecular Variants against Pathological Hallmarks of Alzheimer's Disease.Pharmaceuticals (Basel, Switzerland) · 2020Review
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Missorting of MAPT/Tau represents one of the early signs of neurodegeneration in Alzheimer disease. The triggers for this are still a matter of debate. Here we investigated the sorting mechanisms of endogenous MAPT in mature primary neurons using microfluidic chambers (MFCs) where cell compartments can be observed separately. Blocking protein degradation pathways with proteasomal or autophagy inhibitors dramatically increased the missorting of MAPT in dendrites on the neuritic side, suggesting that degradation of MAPT in dendrites is a major determinant for the physiological axonal distribution of MAPT. Such missorted dendritic MAPT differed in its phosphorylation pattern from axonal MAPT. By contrast, enhancing autophagy or proteasomal pathways strongly reduced MAPT missorting, thereby confirming the role of protein degradation pathways in the polar distribution of MAPT. Dendritic missorting of MAPT by blocking protein degradation resulted in the loss of spines but not in overall cell toxicity. Inhibition of local protein synthesis in dendrites eliminated the missorting of MAPT, indicating that the accumulation of dendritic MAPT is locally generated. In support of this, a substantial fraction of Mapt/Tau mRNA was detected in dendrites. Taken together, our results indicate that the autophagy and proteasomal pathways play important roles in fine-tuning dendritic MAPT levels and thereby prevent synaptic toxicity caused by MAPT accumulation. Abbreviations Ani: anisomycin; Baf: bafilomycin A
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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.