ArticleHuman molecular genetics2021
Disulfide bond formation in microtubule-associated tau protein promotes tau accumulation and toxicity in vivo.
Article in Human molecular genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 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
24 citing papers in PubMed, 39 citations in OpenAlex.
- Oxidative stress impairs processive motility of the axonal transport motor KIF1A.The Journal of biological chemistry · 2026Article
- Cysteines are critical determinants of spontaneous and seeded tau aggregation in cells.Research square · 2026Article
- Cysteines are critical determinants of spontaneous and seeded tau aggregation in cells.bioRxiv : the preprint server for biology · 2026Article
- Tau oligomers modulate synapse fate by eliciting progressive bipartite synapse dysregulation and synapse loss.Molecular neurodegeneration · 2026Article
- Dysfunctional Chondroitin 4-Cells · 2025Article
- Pathological Disulfide Bond Crosslinking: Molecular Insights into Amyloidogenesis and Diseases Progression.Chembiochem : a European journal of chemical biology · 2025Review
- Monitoring the Dynamics of Alzheimer's Disease Biomarkers and the APOE-Tau Axis via Human Cerebral Organoids with Immuno-SERS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Antioxidative effects of phytoaromatic compounds on the cysteine of the SKCGS peptide as a critical aggregation domain of tau.Scientific reports · 2025Article
- Oxidative Stress: Pathological Driver in Chronic Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2025Review
- ESCRT-I and PTPN23 mediate microautophagy of ubiquitylated tau aggregates.The Journal of cell biology · 2025Article
- Non-enzymatic posttranslational protein modifications in protein aggregation and neurodegenerative diseases.RSC chemical biology · 2025Review
- Cellular Uptake of Tau Aggregates Triggers Disulfide Bond Formation in Four-Repeat Tau Monomers.ACS chemical neuroscience · 2025Article
- Oxidative stress: from molecular studies to clinical intervention strategies.Frontiers in molecular biosciences · 2025Review
- Tau is required for glial lipid droplet formation and resistance to neuronal oxidative stress.Nature neuroscience · 2024Article
- Impaired Mitochondrial Energy Metabolism Regulated byMetabolites · 2024Article
- Exploring Tau Fibril-Disaggregating and Antioxidating Molecules Binding to Membrane-Bound Amyloid Oligomers Using Machine Learning-Enhanced Docking and Molecular Dynamics.Molecules (Basel, Switzerland) · 2024Article
- Identification of Tau Toxicity Modifiers in the Drosophila Eye.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Oxidative Stress Occurs Prior to Amyloid Aβ Plaque Formation and Tau Phosphorylation in Alzheimer's Disease: Role of Glutathione and Metal Ions.ACS chemical neuroscience · 2023Review
- In Situ Raman Study of Neurodegenerated Human Neuroblastoma Cells Exposed to Outer-Membrane Vesicles Isolated fromInternational journal of molecular sciences · 2023Article
- Targeting the Cysteine Redox Proteome in Parkinson's Disease: The Role of Glutathione Precursors and Beyond.Antioxidants (Basel, Switzerland) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
Abstract
Accumulation of microtubule-associated tau protein is thought to cause neuron loss in a group of neurodegenerative diseases called tauopathies. In diseased brains, tau molecules adopt pathological structures that propagate into insoluble forms with disease-specific patterns. Several types of posttranslational modifications in tau are known to modulate its aggregation propensity in vitro, but their influence on tau accumulation and toxicity at the whole-organism level has not been fully elucidated. Herein, we utilized a series of transgenic Drosophila models to compare systematically the toxicity induced by five tau constructs with mutations or deletions associated with aggregation, including substitutions at seven disease-associated phosphorylation sites (S7A and S7E), deletions of PHF6 and PHF6* sequences (ΔPHF6 and ΔPHF6*), and substitutions of cysteine residues in the microtubule binding repeats (C291/322A). We found that substitutions and deletions resulted in different patterns of neurodegeneration and accumulation, with C291/322A having a dramatic effect on both tau accumulation and neurodegeneration. These cysteines formed disulfide bonds in mouse primary cultured neurons and in the fly retina, and stabilized tau proteins. Additionally, they contributed to tau accumulation under oxidative stress. We also found that each of these cysteine residues contributes to the microtubule polymerization rate and microtubule levels at equilibrium, but none of them affected tau binding to polymerized microtubules. Since tau proteins expressed in the Drosophila retina are mostly present in the early stages of tau filaments self-assembly, our results suggest that disulfide bond formation by these cysteine residues could be attractive therapeutic targets.
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.