ArticleFrontiers in cellular neuroscience2019
Distinct Conformations, Aggregation and Cellular Internalization of Different Tau Strains.
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 24 papers.
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Who cites it
24 citing papers in PubMed, 42 citations in OpenAlex.
- Differences in the soluble and insoluble proteome between primary tauopathies.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Tau aggregation induces cell death in iPSC-derived neurons.Aging brain · 2025Article
- Modulation of Amyloid and Tau Aggregation to Alleviate Cognitive Impairment in a Transgenic Mouse Model of Alzheimer's Disease.ACS pharmacology & translational science · 2024Article
- Identification of high-performing antibodies for the reliable detection of Tau proteoforms by Western blotting and immunohistochemistry.Acta neuropathologica · 2024Article
- Novel ultrasensitive immunoassay for the selective quantification of tau oligomers and related soluble aggregates.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Article
- Prion-like strain effects in tauopathies.Cell and tissue research · 2023Review
- Connectome-based biophysics models of Alzheimer's disease diagnosis and prognosis.Translational research : the journal of laboratory and clinical medicine · 2023Review
- A new electrochemical method that mimics phosphorylation of the core tau peptide K18 enables kinetic and structural analysis of intermediates and assembly.The Journal of biological chemistry · 2023Article
- A Validated Method to Prepare Stable Tau Oligomers.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Functional Applications of Stable Tau Oligomers in Cell Biology and Electrophysiology Studies.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Blood phospho-tau in Alzheimer disease: analysis, interpretation, and clinical utility.Nature reviews. Neurology · 2022Review
- Heparan Sulfate Proteoglycans (HSPGs) Serve as the Mediator Between Monomeric Tau and Its Subsequent Intracellular ERK1/2 Pathway Activation.Journal of molecular neuroscience : MN · 2022Article
- A surrogate marker for very early-stage tau pathology is detectable by molecular magnetic resonance imaging.Theranostics · 2022Article
- Truncating tau reveals different pathophysiological actions of oligomers in single neurons.Communications biology · 2021Article
- Dissecting the Binding Profile of PET Tracers to Corticobasal Degeneration Tau Fibrils.ACS chemical neuroscience · 2021Article
- RNA Dynamics in Alzheimer's Disease.Molecules (Basel, Switzerland) · 2021Review
- Fisetin inhibits tau aggregation by interacting with the protein and preventing the formation of β-strands.International journal of biological macromolecules · 2021Article
- The AD tau core spontaneously self-assembles and recruits full-length tau to filaments.Cell reports · 2021Article
- Effects of pharmacological modulators of α-synuclein and tau aggregation and internalization.Scientific reports · 2020Article
- An elongated tract of polyQ in the carboxyl‑terminus of human α1A calcium channel induces cell apoptosis by nuclear translocation.Oncology reports · 2020Article
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The inter-cellular propagation of tau aggregates in several neurodegenerative diseases involves, in part, recurring cycles of extracellular tau uptake, initiation of endogenous tau aggregation, and extracellular release of at least part of this protein complex. However, human brain tau extracts from diverse tauopathies exhibit variant or "strain" specificity in inducing inter-cellular propagation in both cell and animal models. It is unclear if these distinctive properties are affected by disease-specific differences in aggregated tau conformation and structure. We have used a combined structural and cell biological approach to study if two frontotemporal dementia (FTD)-associated pathologic mutations, V337M and N279K, affect the aggregation, conformation and cellular internalization of the tau four-repeat domain (K18) fragment. In both heparin-induced and native-state aggregation experiments, each FTD variant formed soluble and fibrillar aggregates with remarkable morphological and immunological distinctions from the wild type (WT) aggregates. Exogenously applied oligomers of the FTD tau-K18 variants (V337M and N279K) were significantly more efficiently taken up by SH-SY5Y neuroblastoma cells than WT tau-K18, suggesting mutation-induced changes in cellular internalization. However, shared internalization mechanisms were observed: endocytosed oligomers were distributed in the cytoplasm and nucleus of SH-SY5Y cells and the neurites and soma of human induced pluripotent stem cell-derived neurons, where they co-localized with endogenous tau and the nuclear protein nucleolin. Altogether, evidence of conformational and aggregation differences between WT and disease-mutated tau K18 is demonstrated, which may explain their distinct cellular internalization potencies. These findings may account for critical aspects of the molecular pathogenesis of tauopathies involving WT and mutated tau.
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