{"entity": "researcher", "timestamp": "2026-08-23T09:27:05.271Z", "family": "Linse", "given": "Sara", "initials": "S", "orcid": "0000-0001-9629-7109", "affiliations": ["Division of Biochemistry and Structural Biology, Department of Chemistry, Lund University, SE-22100 Lund, Sweden."], "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/researcher/ed0f1aa3c40c44b687cb4be5082f0966.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/researcher/ed0f1aa3c40c44b687cb4be5082f0966"}}, "publications": [{"entity": "publication", "iuid": "1bb2b4985c7f4216a57540980b652175", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/1bb2b4985c7f4216a57540980b652175.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/1bb2b4985c7f4216a57540980b652175"}}, "title": "A\u03b2 Oligomer Dissociation Is Catalyzed by Fibril Surfaces.", "authors": [{"family": "Dear", "given": "Alexander J", "initials": "AJ", "orcid": "0000-0003-3055-607X", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/02101a4ade564eb4a2229ffc36fc4b65.json"}}, {"family": "Thacker", "given": "Dev", "initials": "D", "orcid": "0000-0001-6171-9703", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/50d270b853734b82858a09bb9d8d65f8.json"}}, {"family": "Wennmalm", "given": "Stefan", "initials": "S"}, {"family": "Ortigosa-Pascual", "given": "Lei", "initials": "L", "orcid": "0000-0003-0656-9225", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/43a6713f00c64b37a1ef718f637c1df5.json"}}, {"family": "Andrzejewska", "given": "Ewa A", "initials": "EA"}, {"family": "Meisl", "given": "Georg", "initials": "G", "orcid": "0000-0002-6562-7715", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/401911096b9b4b83be3b4a1838aed993.json"}}, {"family": "Linse", "given": "Sara", "initials": "S", "orcid": "0000-0001-9629-7109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ed0f1aa3c40c44b687cb4be5082f0966.json"}}, {"family": "Knowles", "given": "Tuomas P J", "initials": "TPJ", "orcid": "0000-0002-7879-0140", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/3cc16b724a664d0a80996105055eb387.json"}}], "type": "journal article", "published": "2024-06-05", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "15", "issue": "11", "pages": "2296-2307", "issn-l": "1948-7193"}, "abstract": "Oligomeric assemblies consisting of only a few protein subunits are key species in the cytotoxicity of neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases. Their lifetime in solution and abundance, governed by the balance of their sources and sinks, are thus important determinants of disease. While significant advances have been made in elucidating the processes that govern oligomer production, the mechanisms behind their dissociation are still poorly understood. Here, we use chemical kinetic modeling to determine the fate of oligomers formed in vitro and discuss the implications for their abundance in vivo. We discover that oligomeric species formed predominantly on fibril surfaces, a broad class which includes the bulk of oligomers formed by the key Alzheimer's disease-associated A\u03b2 peptides, also dissociate overwhelmingly on fibril surfaces, not in solution as had previously been assumed. We monitor this \"secondary nucleation in reverse\" by measuring the dissociation of A\u03b242 oligomers in the presence and absence of fibrils via two distinct experimental methods. Our findings imply that drugs that bind fibril surfaces to inhibit oligomer formation may also inhibit their dissociation, with important implications for rational design of therapeutic strategies for Alzheimer's and other amyloid diseases.", "doi": "10.1021/acschemneuro.4c00127", "pmid": "38785363", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC11157482"}], "notes": [], "created": "2026-08-21T11:36:01.307Z", "modified": "2026-08-21T11:36:01.536Z"}, {"entity": "publication", "iuid": "e4686060e200429a8c26195ef15b5640", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/e4686060e200429a8c26195ef15b5640.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/e4686060e200429a8c26195ef15b5640"}}, "title": "Cooperativity of \u03b1-Synuclein Binding to Lipid Membranes.", "authors": [{"family": "Makasewicz", "given": "Katarzyna", "initials": "K", "orcid": "0000-0001-7224-5750", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/633bf8178b8b4afd9523466931f4f1d7.json"}}, {"family": "Wennmalm", "given": "Stefan", "initials": "S"}, {"family": "Stenqvist", "given": "Bj\u00f6rn", "initials": "B", "orcid": "0000-0002-9099-0663", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a146f6aabeb84350b47c49897d7a68fc.json"}}, {"family": "Fornasier", "given": "Marco", "initials": "M"}, {"family": "Andersson", "given": "Alexandra", "initials": "A"}, {"family": "J\u00f6nsson", "given": "Peter", "initials": "P", "orcid": "0000-0003-2994-8017", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/964d7a586e1544e18dc06ee9634ed261.json"}}, {"family": "Linse", "given": "Sara", "initials": "S", "orcid": "0000-0001-9629-7109", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/ed0f1aa3c40c44b687cb4be5082f0966.json"}}, {"family": "Sparr", "given": "Emma", "initials": "E", "orcid": "0000-0001-8343-9657", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/a692e20cc68741be9221c981481f2a4d.json"}}], "type": "journal article", "published": "2021-06-16", "journal": {"title": "ACS Chem Neurosci", "issn": "1948-7193", "volume": "12", "issue": "12", "pages": "2099-2109", "issn-l": "1948-7193"}, "abstract": "Cooperative binding is a key feature of metabolic pathways, signaling, and transport processes. It provides tight regulation over a narrow concentration interval of a ligand, thus enabling switching to be triggered by small concentration variations. The data presented in this work reveal strong positive cooperativity of \u03b1-synuclein binding to phospholipid membranes. Fluorescence cross-correlation spectroscopy, confocal microscopy, and cryo-TEM results show that in excess of vesicles \u03b1-synuclein does not distribute randomly but binds only to a fraction of all available vesicles. Furthermore, \u03b1-synuclein binding to a supported lipid bilayer observed with total internal reflection fluorescence microscopy displays a much steeper dependence of bound protein on total protein concentration than expected for independent binding. The same phenomenon was observed in the case of \u03b1-synuclein binding to unilamellar vesicles of sizes in the nm and \u03bcm range as well as to flat supported lipid bilayers, ruling out that nonuniform binding of the protein is governed by differences in membrane curvature. Positive cooperativity of \u03b1-synuclein binding to lipid membranes means that the affinity of the protein to a membrane is higher where there is already protein bound compared to a bare membrane. The phenomenon described in this work may have implications for \u03b1-synuclein function in synaptic transmission and other membrane remodeling events.", "doi": "10.1021/acschemneuro.1c00006", "pmid": "34076426", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC8291482"}], "notes": [], "created": "2026-08-21T11:35:48.735Z", "modified": "2026-08-21T11:35:48.925Z"}]}