Tau Oligomers Impair Artificial Membrane Integrity and Cellular Viability
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The microtubule-associated protein Tau is mainly expressed in neurons, where it binds and stabilizes microtubules. In Alzheimer disease and other tauopathies, Tau protein has a reduced affinity toward microtubules. As a consequence, Tau protein detaches from microtubules and eventually aggregates into β-sheet-containing filaments. The fibrillization of monomeric Tau to filaments is a multistep process that involves the formation of various aggregates, including spherical and protofibrillar oligomers. Previous concepts, primarily developed for Aβ and α-synuclein, propose these oligomeric intermediates as the primary cytotoxic species mediating their deleterious effects through membrane permeabilization. In the present study, we thus analyzed whether this concept can also be applied to Tau protein. To this end, viability and membrane integrity were assessed on SH-SY5Y neuroblastoma cells and artificial phospholipid vesicles, treated with Tau monomers, Tau aggregation intermediates, or Tau fibrils. Our findings suggest that oligomeric Tau aggregation intermediates are the most toxic compounds of Tau fibrillogenesis, which effectively decrease cell viability and increase phospholipid vesicle leakage. Our data integrate Tau protein into the class of amyloidogenic proteins and enforce the hypothesis of a common toxicity-mediating mechanism for amyloidogenic proteins.
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Tau-mediated neurodegeneration arises from multiple pathological mechanisms including loss of normal function, gain of toxic function, aggregation, and mislocalization.
“Tau-mediated neurodegeneration arises from multiple pathological mechanisms, including loss of normal function [37–42], gain of toxic function [43–46], aggregation [44, 47–49], and mislocalization [50–52].”
From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [46]
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Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease
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- Authors
- Flach, K., Hilbrich, I., Schiffmann, A., Gärtner, U., Krüger, M., Leonhardt, M., Waschipky, H., Wick, L., Arendt, T., & Holzer, M.
- Affiliations
- Leipzig University (DE)
- Helmholtz Centre for Environmental Research (DE)
- Corresponding author
- Holzer, Max
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2012-12
- Volume
- 287
- Issue
- 52
- Pages
- 43223-43233
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC3527910
- OpenAlex
- W1971677273
- Cited by
- 188
- References
- 7
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 8 · 2023: 5 · 2022: 20 · 2021: 21 · 2020: 24 · 2019: 16 · 2018: 18 · 2017: 21 · 2016: 8 · 2015: 17 · 2014: 5 · 2013: 9
- FWCI
- 6.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Aldose Reductase and Taurine
- Keywords
- tau protein, tau oligomers, protofibrils, membrane permeabilization, membrane integrity, cell viability, amyloidogenic proteins, Alzheimer's disease, tauopathy, neurotoxicity, SH-SY5Y cells
- MeSH terms
- Amyloid, Cell Membrane, Cell Membrane Permeability, Cell Survival, Humans, Phospholipids, tau Proteins, Protein Structure, Secondary, Protein Structure, Quaternary, Tauopathies, Cell Line, Tumor
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