ArticleThe Journal of biological chemistry2017
Modulation of the extent of structural heterogeneity in α-synuclein fibrils by the small molecule thioflavin T.
Article in The Journal of biological chemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 34 citations in OpenAlex.
- Human and Mouse Alpha-Synuclein Fibrillation: Impact on h-FTAA Binding and Advancing Strain-Specific Biomarkers in PD Animal Models.International journal of molecular sciences · 2026Article
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- Modulation of the Fibrillation Kinetics and Morphology of a Therapeutic Peptide by Cucurbit[7]uril.Molecular pharmaceutics · 2023Article
- Monitoring α-synuclein aggregation.Neurobiology of disease · 2023Review
- Effects of Mutations and Post-Translational Modifications on α-Synuclein In Vitro Aggregation.Journal of molecular biology · 2022Review
- (De)stabilization of Alpha-Synuclein Fibrillary Aggregation by Charged and Uncharged Surfactants.International journal of molecular sciences · 2021Article
- New strategies for fluorescently labeling proteins in the study of amyloids.Current opinion in chemical biology · 2021Review
- The Lys 280 → Gln mutation mimicking disease-linked acetylation of Lys 280 in tau extends the structural core of fibrils and modulates their catalytic properties.Protein science : a publication of the Protein Society · 2021Article
- Extent of N-terminus exposure of monomeric alpha-synuclein determines its aggregation propensity.Nature communications · 2020Article
- Triphala inhibits alpha-synuclein fibrillization and their interaction study by NMR provides insights into the self-association of the protein.RSC advances · 2019Article
- β-Amyloid aggregation and heterogeneous nucleation.Protein science : a publication of the Protein Society · 2019Review
- Tau Interacts with the C-Terminal Region of α-Synuclein, Promoting Formation of Toxic Aggregates with Distinct Molecular Conformations.Biochemistry · 2019Article
- A Protofilament-Protofilament Interface in the Structure of Mouse α-Synuclein Fibrils.Biophysical journal · 2018Article
- Pre-aggregation kinetics and intermediates of α-synuclein monitored by the ESIPT probe 7MFE.European biophysics journal : EBJ · 2018Article
- Fluorescence spectroscopy reveals N-terminal order in fibrillar forms of α-synuclein.Chemical communications (Cambridge, England) · 2018Article
- Using mass spectrometry-based methods to understand amyloid formation and inhibition of alpha-synuclein and amyloid beta.Mass spectrometry reviewsReview
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The transition of intrinsically disordered, monomeric α-synuclein into β-sheet-rich oligomers and fibrils is associated with multiple neurodegenerative diseases. Fibrillar aggregates possessing distinct structures that differ in toxicity have been observed in different pathological phenotypes. Understanding the mechanism of the formation of various fibril polymorphs with differing cytotoxic effects is essential for determining how the aggregation reaction could be modulated to favor nontoxic fibrils over toxic fibrils. In this study, two morphologically different α-synuclein fibrils, one helical and the other ribbon-like, are shown to form together. Surprisingly, a widely used small molecule for probing aggregation reactions, thioflavin T (ThT), was found to tune the structural heterogeneity found in the fibrils. The ribbon-like fibrils formed in the presence of ThT were found to have a longer structural core than the helical fibrils formed in the absence of ThT. The ribbon-like fibrils are also more toxic to cells. By facilitating the formation of ribbon-like fibrils over helical fibrils, ThT reduced the extent of fibril polymorphism. This study highlights the role of a small molecule such as ThT in selectively favoring the formation of a specific type of fibril by binding to aggregates formed early on one of multiple pathways, thereby altering the structural core and external morphology of the fibrils formed.
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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.