ArticleThe Journal of biological chemistry2012
S100A6 amyloid fibril formation is calcium-modulated and enhances superoxide dismutase-1 (SOD1) aggregation.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Unraveling the regulatory nexus of aggrephagy in ALS: identification of novel candidate biomarkers and molecular triggers.Metabolic brain disease · 2026Article
- Multifaceted roles of S100A6 in neurological disorders: expression, interaction networks, and clinical implications.Frontiers in pharmacology · 2026Review
- Calcium-Dependent S100A8 Amyloid Fibril Formation via S100A1-Mediated Transient Interaction.ACS chemical neuroscience · 2025Article
- Neuroinflammation generated by HIV-infected microglia promotes dysfunction and death of neurons in human brain organoids.PNAS nexus · 2024Article
- Secondary Modification of S100B Influences Anti Amyloid-β Aggregation Activity and Alzheimer's Disease Pathology.International journal of molecular sciences · 2024Article
- Disassembly of Amyloid Fibril with Infrared Free Electron Laser.International journal of molecular sciences · 2023Review
- Amyloid adhesin production in activated sludge is enhanced in lab-scale sequencing batch reactors: Feeding regime impacts microbial community and amyloid distribution.Water research X · 2022Article
- Dynamic interactions and CaNature communications · 2021Article
- Article
- S100A6 and Its Brain Ligands in Neurodegenerative Disorders.International journal of molecular sciences · 2020Review
- Neuroanatomical Quantitative Proteomics Reveals Common Pathogenic Biological Routes between Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD).International journal of molecular sciences · 2018Review
- S100A9-Driven Amyloid-Neuroinflammatory Cascade in Traumatic Brain Injury as a Precursor State for Alzheimer's Disease.Scientific reports · 2018Article
- Co-aggregation of pro-inflammatory S100A9 with α-synuclein in Parkinson's disease: ex vivo and in vitro studies.Journal of neuroinflammation · 2018Article
- S100A6 protein: functional roles.Cellular and molecular life sciences : CMLS · 2017Review
- Mutations in the vesicular trafficking protein annexin A11 are associated with amyotrophic lateral sclerosis.Science translational medicine · 2017Article
- Zinc Binding to S100B Affords Regulation of Trace Metal Homeostasis and Excitotoxicity in the Brain.Frontiers in molecular neuroscience · 2017Article
- Selective inhibition of aggregation/fibrillation of bovine serum albumin by osmolytes: Mechanistic and energetics insights.PloS one · 2017Article
- Staphylococcal Bap Proteins Build Amyloid Scaffold Biofilm Matrices in Response to Environmental Signals.PLoS pathogens · 2016Article
- Characterization of Protein Structural Changes in Living Cells Using Time-Lapsed FTIR Imaging.Analytical chemistry · 2015Article
- Targeting miR-155 restores abnormal microglia and attenuates disease in SOD1 mice.Annals of neurology · 2015Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
S100A6 is a small EF-hand calcium- and zinc-binding protein involved in the regulation of cell proliferation and cytoskeletal dynamics. It is overexpressed in neurodegenerative disorders and a proposed marker for Amyotrophic Lateral Sclerosis (ALS). Following recent reports of amyloid formation by S100 proteins, we investigated the aggregation properties of S100A6. Computational analysis using aggregation predictors Waltz and Zyggregator revealed increased propensity within S100A6 helices H(I) and H(IV). Subsequent analysis of Thioflavin-T binding kinetics under acidic conditions elicited a very fast process with no lag phase and extensive formation of aggregates and stacked fibrils as observed by electron microscopy. Ca(2+) exerted an inhibitory effect on the aggregation kinetics, which could be reverted upon chelation. An FT-IR investigation of the early conformational changes occurring under these conditions showed that Ca(2+) promotes anti-parallel β-sheet conformations that repress fibrillation. At pH 7, Ca(2+) rendered the fibril formation kinetics slower: time-resolved imaging showed that fibril formation is highly suppressed, with aggregates forming instead. In the absence of metals an extensive network of fibrils is formed. S100A6 oligomers, but not fibrils, were found to be cytotoxic, decreasing cell viability by up to 40%. This effect was not observed when the aggregates were formed in the presence of Ca(2+). Interestingly, native S1006 seeds SOD1 aggregation, shortening its nucleation process. This suggests a cross-talk between these two proteins involved in ALS. Overall, these results put forward novel roles for S100 proteins, whose metal-modulated aggregation propensity may be a key aspect in their physiology and function.
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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.