ArticleProtein engineering, design & selection : PEDS2016
Transthyretin variants with improved inhibition of β-amyloid aggregation.
Article in Protein engineering, design & selection : PEDS, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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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
17 citing papers in PubMed, 28 citations in OpenAlex.
- Unravelling the myriad physiologic roles of transthyretin: critical considerations for treating transthyretin amyloidosis.Annals of medicine · 2025Review
- Age-related decline in protein turnover highlights cystatin C dysfunction and links proteostasis collapse to neuroinflammation in the murine cortex.Biogerontology · 2025Article
- Article
- The Regulatory Mechanism of Transthyretin Irreversible Aggregation through Liquid-to-Solid Phase Transition.International journal of molecular sciences · 2023Article
- Endogenous Human Proteins Interfering with Amyloid Formation.Biomolecules · 2022Review
- Neuroserpin and transthyretin are extracellular chaperones that preferentially inhibit amyloid formation.Science advances · 2021Article
- The interaction of zinc with the multi-functional plasma thyroid hormone distributor protein, transthyretin: evolutionary and cross-species comparative aspects.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2021Review
- Mechanisms of Transthyretin Inhibition of IAPP Amyloid Formation.Biomolecules · 2021Article
- Apolipoprotein E Interferes with IAPP Aggregation and Protects Pericytes from IAPP-Induced Toxicity.Biomolecules · 2020Article
- Morphological analysis of Apolipoprotein E binding to Aβ Amyloid using a combination of Surface Plasmon Resonance, Immunogold Labeling and Scanning Electron Microscopy.BMC biotechnology · 2019Article
- Plasma Transthyretin as a Predictor of Amnestic Mild Cognitive Impairment Conversion to Dementia.Scientific reports · 2019Article
- Copper mediated amyloid-β binding to Transthyretin.Scientific reports · 2018Article
- Retinol-Binding Protein Interferes with Transthyretin-Mediated β-Amyloid Aggregation Inhibition.Biochemistry · 2018Article
- Inhibition of amyloid beta fibril formation by monomeric human transthyretin.Protein science : a publication of the Protein Society · 2018Article
- Inhibition of curli assembly andProceedings of the National Academy of Sciences of the United States of America · 2017Article
- Cerebrospinal Fluid Proteins as Regulators of Beta-amyloid Aggregation and Toxicity.Israel journal of chemistry · 2017Article
- Transthyretin and BRICHOS: The Paradox of Amyloidogenic Proteins with Anti-Amyloidogenic Activity for Aβ in the Central Nervous System.Frontiers in neuroscience · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Aggregation of β-amyloid (Aβ) is widely believed to cause neuronal dysfunction in Alzheimer's disease. Transthyretin (TTR) binds to Aβ and inhibits its aggregation and neurotoxicity. TTR is a homotetrameric protein, with each monomer containing a short α-helix and two anti-parallel β-sheets. Dimers pack into tetramers to form a hydrophobic cavity. Here we report the discovery of a TTR mutant, N98A, that was more effective at inhibiting Aβ aggregation than wild-type (WT) TTR, although N98A and WT bound Aβ equally. The N98A mutation is located on a flexible loop distant from the putative Aβ-binding sites and does not alter secondary and tertiary structures nor prevent correct assembly into tetramers. Under non-physiological conditions, N98A tetramers were kinetically and thermodynamically less stable than WT, suggesting a difference in the tetramer folded structure. In vivo, the lone cysteine in TTR is frequently modified by S-cysteinylation or S-sulfonation. Like the N98A mutation, S-cysteinylation of TTR modestly decreased tetramer stability and increased TTR's effectiveness at inhibiting Aβ aggregation. Collectively, these data indicate that a subtle change in TTR tetramer structure measurably increases TTR's ability to inhibit Aβ aggregation.
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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.