ArticleThe Journal of biological chemistry2017
Insights into the mechanism of cystatin C oligomer and amyloid formation and its interaction with β-amyloid.
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 21 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.
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Who cites it
21 citing papers in PubMed, 29 citations in OpenAlex.
- Cystatin C and its Role in the Neuro-Glial-Vascular Unit: Implications for Cerebrovascular Diseases and Neurodegeneration.Neuroscience bulletin · 2026Review
- Article
- Exosome-Mediated Delivery of Amyloid Beta Modulators: A Potential Therapeutic Strategy for Alzheimer's Disease.Molecular neurobiology · 2025Review
- Cystatins: unravelling the biological implications for neuroprotection.Archives of medical science : AMS · 2024Article
- Human cystatin C induces the disaggregation process of selected amyloid beta peptides: a structural and kinetic view.Scientific reports · 2023Article
- Effect of Ovocystatin on Amyloid β 1-42 Aggregation-In Vitro Studies.International journal of molecular sciences · 2023Article
- Oligomerization of Human Cystatin C-An Amyloidogenic Protein: An Analysis of Small Oligomeric Subspecies.International journal of molecular sciences · 2022Article
- The relationship between plasma cystatin C, mortality and acute respiratory distress syndrome subphenotype in the HARP-2 trial.Critical care and resuscitation : journal of the Australasian Academy of Critical Care Medicine · 2022Article
- Is amyloid fibrillation related to 3D domain swapping for the C-terminal domain of SARS-CoV main protease?International journal of biological macromolecules · 2022Article
- Aggregation of Cystatin C Changes Its Inhibitory Functions on Protease Activities and Amyloid β Fibril Formation.International journal of molecular sciences · 2021Article
- NAC blocks Cystatin C amyloid complex aggregation in a cell system and in skin of HCCAA patients.Nature communications · 2021Article
- TDP-43 interacts with amyloid-β, inhibits fibrillization, and worsens pathology in a model of Alzheimer's disease.Nature communications · 2020Article
- Structural Characterization of Covalently Stabilized Human Cystatin C Oligomers.International journal of molecular sciences · 2020Article
- Metal ions and redox balance regulate distinct amyloid-like aggregation pathways of GAPR-1.Scientific reports · 2019Article
- The Functional Mammalian CRES (Cystatin-Related Epididymal Spermatogenic) Amyloid is Antiparallel β-Sheet Rich and Forms a Metastable Oligomer During Assembly.Scientific reports · 2019Article
- Studies of the oligomerisation mechanism of a cystatin-based engineered protein scaffold.Scientific reports · 2019Article
- The domain swapping of human cystatin C induced by synchrotron radiation.Scientific reports · 2019Article
- Mycobacterium tuberculosis CarD, an essential global transcriptional regulator forms amyloid-like fibrils.Scientific reports · 2018Article
- A mechanistic model to predict effects of cathepsin B and cystatin C on β-amyloid aggregation and degradation.The Journal of biological chemistry · 2017Article
- Insights into protein misfolding and aggregation enabled by solid-state NMR spectroscopy.Solid state nuclear magnetic resonance · 2017Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Cystatin C (CysC) is a versatile and ubiquitously-expressed member of the cysteine protease inhibitor family that is present at notably high concentrations in cerebrospinal fluid. Under mildly denaturing conditions, CysC forms inactive domain-swapped dimers. A destabilizing mutation, L68Q, increases the rate of domain-swapping and causes a fatal amyloid disease, hereditary cystatin C amyloid angiopathy. Wild-type (wt) CysC will also aggregate into amyloid fibrils under some conditions. Propagated domain-swapping has been proposed as the mechanism by which CysC fibrils grow. We present evidence that a CysC mutant, V57N, stabilized against domain-swapping, readily forms fibrils, contradicting the propagated domain-swapping hypothesis. Furthermore, in physiological buffer, wt CysC can form oligomers without undergoing domain-swapping. These non-swapped oligomers are identical in secondary structure to CysC monomers and completely retain protease inhibitory activity. However, unlike monomers or dimers, the oligomers bind fluorescent dyes that indicate they have characteristics of pre-amyloid aggregates. Although these oligomers appear to be a pre-amyloid assembly, they are slower than CysC monomers to form fibrils. Fibrillation of CysC therefore likely initiates from the monomer and does not require domain-swapping. The non-swapped oligomers likely represent a dead-end offshoot of the amyloid pathway and must dissociate to monomers prior to rearranging to amyloid fibrils. These prefibrillar CysC oligomers were potent inhibitors of aggregation of the Alzheimer's-related peptide, β-amyloid. This result illustrates an example where heterotypic interactions between pre-amyloid oligomers prevent the homotypic interactions that would lead to mature amyloid fibrils.
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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.