ArticleBiochemistry2009
Pseudohyperphosphorylation causing AD-like changes in tau has significant effects on its polymerization.
Article in Biochemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 47 citations in OpenAlex.
- Heat shock proteins (Hsp70 and Hsp90) in neurodegeneration: pathogenic roles and therapeutic potential.Frontiers in aging neuroscience · 2026Review
- Navigating the landscape of protein folding and proteostasis: from molecular chaperones to therapeutic innovations.Signal transduction and targeted therapy · 2025Review
- Polyamination with spermidine enhances pathogenic tau conformations while reducing filamentous aggregate formation in vitro.The Biochemical journal · 2025Article
- Biochemical approaches to assess the impact of post-translational modifications on pathogenic tau conformations using recombinant protein.Biochemical Society transactions · 2024Review
- Phosphomimetics at Ser199/Ser202/Thr205 in Tau Impairs Axonal Transport in Rat Hippocampal Neurons.Molecular neurobiology · 2023Article
- The identities of insulin signaling pathway are affected by overexpression of Tau and its phosphorylation form.Frontiers in aging neuroscience · 2022Article
- Prion-Like Propagation Mechanisms in Tauopathies and Traumatic Brain Injury: Challenges and Prospects.Biomolecules · 2020Review
- Tau Ser208 phosphorylation promotes aggregation and reveals neuropathologic diversity in Alzheimer's disease and other tauopathies.Acta neuropathologica communications · 2020Article
- Dynamic behaviors of α-synuclein and tau in the cellular context: New mechanistic insights and therapeutic opportunities in neurodegeneration.Neurobiology of disease · 2019Review
- Endogenous oligodendroglial alpha-synuclein and TPPP/p25α orchestrate alpha-synuclein pathology in experimental multiple system atrophy models.Acta neuropathologica · 2019Article
- Article
- Variable tau accumulation in murine models with abnormal prion protein deposits.Journal of the neurological sciences · 2017Article
- Structural evaluations of tau protein conformation: methodologies and approaches.Biochemistry and cell biology = Biochimie et biologie cellulaire · 2017Review
- Tau protein modifications and interactions: their role in function and dysfunction.International journal of molecular sciences · 2014Review
- Protein phosphorylation in neurodegeneration: friend or foe?Frontiers in molecular neuroscience · 2014Review
- Taxol-stabilized microtubules promote the formation of filaments from unmodified full-length Tau in vitro.Molecular biology of the cell · 2012Article
- FTDP-17 tau mutations induce distinct effects on aggregation and microtubule interactions.Biochemistry · 2012Article
- Synergistic influence of phosphorylation and metal ions on tau oligomer formation and coaggregation with α-synuclein at the single molecule level.Molecular neurodegeneration · 2012Article
- Phosphorylation in the amino terminus of tau prevents inhibition of anterograde axonal transport.Neurobiology of aging · 2012Article
- Ubiquitin is associated with early truncation of tau protein at aspartic acid(421) during the maturation of neurofibrillary tangles in Alzheimer's disease.Brain pathology (Zurich, Switzerland) · 2012Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
The microtubule-associated protein tau, in a hyperphosphorylated form, aggregates into insoluble paired-helical filaments (PHFs) in Alzheimer's disease (AD) and other tauopathies. In AD, there is approximately 8 mol of phosphate per mole of tau distributed among approximately 30 PHF phosphorylation sites as compared to 2-3 mol of phosphate per mole in normal brain. In AD, kinases such as glycogen synthase kinase-3beta (GSK-3beta) are believed to be involved in the generation of hyperphosphorylated tau. However, the functional consequences of hyperphosphorylation on the microtubule binding and polymerization of tau are not well understood. To address this question, we have generated pseudohyperphosphorylation mutants consisting of six and seven sites in the proline-rich region and carboxy terminus of tau by amino acid substitution. In addition, several single, double, and triple pseudophosphorylation mutants were also generated. Pseudophosphorylation of tau decreases its affinity for microtubules, and pseudohyperphosphorylated forms of tau do not have significantly decreased levels of microtubule binding as compared to single and double sites. Three pseudohyperphosphorylated forms of tau with altered sodium dodecyl sulfate-polyacrylamide gel electrophoresis migration have a greater effect on its inducer-mediated polymerization, slowing the rate of nucleation and elongation. On the basis of the observations that pseudohyperphosphorylated tau has decreased affinity for microtubules and reduced inducer-initiated rates of nucleation and polymerization, we propose that this combination could be the cause of the increased cytotoxicity of hyperphosphorylated tau in Alzheimer's disease and also explain the potentially beneficial role of tau polymerization and NFT formation.
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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.