ArticleFrontiers in cellular neuroscience2019
Normal and Pathological Tau Uptake Mediated by M1/M3 Muscarinic Receptors Promotes Opposite Neuronal Changes.
Article in Frontiers in cellular neuroscience, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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
38 citing papers in PubMed, 65 citations in OpenAlex.
- Article
- Tau protein: Physiological functions and multifaceted roles in neurodegenerative and psychiatric disorders.Genomic psychiatry : advancing science from genes to society · 2025Article
- Targeted protein degradation with bifunctional molecules as a novel therapeutic modality for Alzheimer's disease & beyond.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025Review
- Distinct regulation of Tau Monomer and aggregate uptake and intracellular accumulation in human neurons.Molecular neurodegeneration · 2024Article
- Cellular and pathological functions of tau.Nature reviews. Molecular cell biology · 2024Review
- Updates in Alzheimer's disease: from basic research to diagnosis and therapies.Translational neurodegeneration · 2024Review
- Tau in neurodegenerative diseases: molecular mechanisms, biomarkers, and therapeutic strategies.Translational neurodegeneration · 2024Review
- Endogenous tau released from humanbioRxiv : the preprint server for biology · 2024Article
- Lung endothelium, tau, and amyloids in health and disease.Physiological reviews · 2024Review
- Moderate regular physical exercise can help in alleviating the systemic impact of schistosomiasis infection on brain cognitive function.Frontiers in immunology · 2024Article
- The Impact of Muscarinic Antagonism on Psychosis-Relevant Behaviors and Striatal [Biomedicines · 2023Article
- Do tau-synaptic long-term depression interactions in the hippocampus play a pivotal role in the progression of Alzheimer's disease?Neural regeneration research · 2023Review
- G protein-coupled receptors in neurodegenerative diseases and psychiatric disorders.Signal transduction and targeted therapy · 2023Review
- Common and Specific Marks of Different Tau Strains Following Intra-Hippocampal Injection of AD, PiD, and GGT Inoculum in hTau Transgenic Mice.International journal of molecular sciences · 2022Article
- The propagation mechanisms of extracellular tau in Alzheimer's disease.Journal of neurology · 2022Review
- Delivery of Intravenously Administered Antibodies Targeting Alzheimer's Disease-Relevant Tau Species into the Brain Based on Receptor-Mediated Transcytosis.Pharmaceutics · 2022Review
- The Fate of Tau Aggregates Between Clearance and Transmission.Frontiers in aging neuroscience · 2022Review
- Importin-Mediated Pathological Tau Nuclear Translocation Causes Disruption of the Nuclear Lamina, TDP-43 Mislocalization and Cell Death.Frontiers in molecular neuroscience · 2022Article
- The role of pathological tau in synaptic dysfunction in Alzheimer's diseases.Translational neurodegeneration · 2021Review
- Astrocytes in Neurodegenerative Diseases: A Perspective from Tauopathy and α-Synucleinopathy.Life (Basel, Switzerland) · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
The microtubule associated protein tau is mainly found in the cell's cytosol but recently it was also shown in the extracellular space. In neurodegenerative diseases, like Alzheimer's disease (AD), pathological tau spreads from neuron to neuron enhancing neurodegeneration. Here, we show that HEK293 cells and neurons in culture uptake extracellular normal and pathological Tau. Muscarinic receptor antagonists atropine and pirenzepine block 80% this uptake. CHO cells do not express these receptors therefore cannot uptake tau, unless transfected with M1 and/or M3 receptor. These results strongly suggest that muscarinic receptors mediate this process. Uptake of normal tau in neurons enhances neuronal process formation but a pseudophosphorylated form of tau (pathological human tau, PH-Tau) disrupts them and accumulates in the somatodendritic compartment. AD hyperphosphorylated tau (AD P-Tau) has similar effects as PH-Tau on cultured neurons. Addition of either PH-Tau or AD P-tau to neuronal cultures induced microglial activation. In conclusion, uptake of extracellular tau is mediated by muscarinic receptors with opposite effects: normal tau stabilizes neurites; whereas pathological tau disrupts this process leading to neurodegeneration.
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.