ArticleProceedings of the National Academy of Sciences of the United States of America2015
pH-induced molecular shedding drives the formation of amyloid fibril-derived oligomers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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Who cites it
60 citing papers in PubMed.
- Spontaneous aging of mature amyloids alters structural stability, cytotoxicity, and susceptibility to biological clearance.Cell death discovery · 2026Article
- Enzymes of physiological amyloidogenesis control pathological amyloid toxicity.Life science alliance · 2026Article
- Physiological responses to mask-associated COFrontiers in public health · 2026Review
- Inorganic Polyphosphate: An Emerging Regulator of Neuronal Bioenergetics and Its Implications in Neuroprotection.Biomolecules · 2025Review
- Broken but not beaten: Challenge of reducing the amyloids pathogenicity by degradation.Journal of advanced research · 2025Review
- On the reversibility of amyloid fibril formation.Biophysics reviews · 2025Review
- In the Beginning: Let Hydration Be Coded in Proteins for Manifestation and Modulation by Salts and Adenosine Triphosphate.International journal of molecular sciences · 2024Review
- Article
- TDP-43 Promotes Amyloid-Beta Toxicity by Delaying Fibril Maturation via Direct Molecular Interaction.ACS chemical neuroscience · 2024Article
- Modulation of Alzheimer's Disease Aβ40 Fibril Polymorphism by the Small Heat Shock Protein αB-Crystallin.Journal of the American Chemical Society · 2024Article
- Structure of cytotoxic amyloid oligomers generated during disaggregation.Journal of biochemistry · 2024Review
- Lung endothelium, tau, and amyloids in health and disease.Physiological reviews · 2024Review
- Molecular mechanisms and emerging therapies in wild-type transthyretin amyloid cardiomyopathy.Heart failure reviews · 2024Review
- Effect of Antihypertensive Drug (Chlorothiazide) on Fibrillation of Lysozyme: A Combined Spectroscopy, Microscopy, and Computational Study.International journal of molecular sciences · 2023Article
- Atomic Resolution Insights into pH Shift Induced Deprotonation Events in LS-Shaped Aβ(1-42) Amyloid Fibrils.Journal of the American Chemical Society · 2023Article
- Identifying Biological and Biophysical Features of Different Maturation States of α-Synuclein Amyloid Fibrils.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Microglia-Astrocyte Communication in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2023Review
- Mechanisms of polyphosphate-induced amyloid fibril formation triggered by breakdown of supersaturation.Biophysics and physicobiology · 2023Article
- Early diagnosis and treatment of Alzheimer's disease by targeting toxic soluble Aβ oligomers.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Amyloid seeding as a disease mechanism and treatment target in transthyretin cardiac amyloidosis.Heart failure reviews · 2022Review
Corrections and comments
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Authors and funding
9 authors.
Funding
Abstract
Amyloid disorders cause debilitating illnesses through the formation of toxic protein aggregates. The mechanisms of amyloid toxicity and the nature of species responsible for mediating cellular dysfunction remain unclear. Here, using β2-microglobulin (β2m) as a model system, we show that the disruption of membranes by amyloid fibrils is caused by the molecular shedding of membrane-active oligomers in a process that is dependent on pH. Using thioflavin T (ThT) fluorescence, NMR, EM and fluorescence correlation spectroscopy (FCS), we show that fibril disassembly at pH 6.4 results in the formation of nonnative spherical oligomers that disrupt synthetic membranes. By contrast, fibril dissociation at pH 7.4 results in the formation of nontoxic, native monomers. Chemical cross-linking or interaction with hsp70 increases the kinetic stability of fibrils and decreases their capacity to cause membrane disruption and cellular dysfunction. The results demonstrate how pH can modulate the deleterious effects of preformed amyloid aggregates and suggest why endocytic trafficking through acidic compartments may be a key factor in amyloid disease.
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