{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T05:03:25Z","timestamp":1788498205625,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T00:00:00Z","timestamp":1671148800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["532\/15"],"award-info":[{"award-number":["532\/15"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Insulin degrading enzyme (IDE) has been detected in the cerebrospinal fluid media and plays a role in encapsulating and degrading the amyloid \u03b2 (A\u03b2) monomer, thus regulating the levels of A\u03b2 monomers. The current work illustrates a first study by which IDE encapsulates polymorphic early-stage A\u03b2 oligomers. The main goal of this study was to investigate the molecular mechanisms of IDE activity on the encapsulated early-stage A\u03b2 dimers: fibril-like and random coil\/\u03b1-helix dimers. Our work led to several findings. First, when the fibril-like A\u03b2 dimer interacts with IDE-C domain, IDE does not impede the contact between the monomers, but plays a role as a \u2018dead-end\u2019 chaperone protein. Second, when the fibril-like A\u03b2 dimer interacts with the IDE-N domain, IDE successfully impedes the contacts between monomers. Third, the inhibitory activity of IDE on random coil\/\u03b1-helix dimers depends on the stability of the dimer. IDE could impede the contacts between monomers in relatively unstable random coil\/\u03b1-helix dimers, but gets hard to impede in stable dimers. However, IDE encapsulates stable dimers and could serve as a \u2018dead-end\u2019 chaperone. Our results examine the molecular interactions between IDE and the dimers, and between the monomers within the dimers. Hence, this study provides insights into the inhibition mechanisms of the primary nucleation of A\u03b2 aggregation and the basic knowledge for rational design to inhibit A\u03b2 aggregation.<\/jats:p>","DOI":"10.3390\/biom12121886","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T02:54:02Z","timestamp":1671159242000},"page":"1886","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Insights into Non-Proteolytic Inhibitory Mechanisms of Polymorphic Early-Stage Amyloid \u03b2 Oligomers by Insulin Degrading Enzyme"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0272-0047","authenticated-orcid":false,"given":"Karina","family":"Abramov-Harpaz","sequence":"first","affiliation":[{"name":"Department of Chemistry, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel"},{"name":"The School of Brain Sciences and Cognition, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel"},{"name":"Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifat","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Ben-Gurion University of the Negev, P.O. Box 653, Beer-Sheva 84105, Israel"},{"name":"The School of Brain Sciences and Cognition, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel"},{"name":"Ilse Katz Institute for Nanoscale Science and Technology, Ben-Gurion University of the Negev, Beer-Sheva 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,12,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2021). 2021 Alzheimer\u2019s disease facts and figures. Alzheimers Dement., 17, 327\u2013406.","DOI":"10.1002\/alz.12328"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1007\/s11064-019-02756-x","article-title":"Powering Amyloid Beta Degrading Enzymes: A Possible Therapy for Alzheimer\u2019s Disease","volume":"44","author":"Sikanyika","year":"2019","journal-title":"Neurochem. 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