{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T01:18:12Z","timestamp":1782523092820,"version":"3.54.5"},"reference-count":107,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,5,8]],"date-time":"2019-05-08T00:00:00Z","timestamp":1557273600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"European Union and Greek national funds through the Operational Program &quot;Competitiveness, Entrepreneurship and Innovation&quot;, under the call \u201cRESEARCH-CREATE-INNOVATE\u201d","award":["T1EDK-00353"],"award-info":[{"award-number":["T1EDK-00353"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Human apolipoprotein E (apoE) is a major component of lipoprotein particles, and under physiological conditions, is involved in plasma cholesterol transport. Human apolipoprotein E found in three isoforms (E2; E3; E4) is a member of a family of apolipoproteins that under pathological conditions are detected in extracellular amyloid depositions in several amyloidoses. Interestingly, the lipid-free apoE form has been shown to be co-localized with the amyloidogenic A\u03b2 peptide in amyloid plaques in Alzheimer\u2019s disease, whereas in particular, the apoE4 isoform is a crucial risk factor for late-onset Alzheimer\u2019s disease. Evidence at the experimental level proves that apoE self-assembles into amyloid fibrilsin vitro, although the misfolding mechanism has not been clarified yet. Here, we explored the mechanistic insights of apoE misfolding by testing short apoE stretches predicted as amyloidogenic determinants by AMYLPRED, and we computationally investigated the dynamics of apoE and an apoE\u2013\u0391\u03b2 complex. Our in vitro biophysical results prove that apoE peptide\u2013analogues may act as the driving force needed to trigger apoE aggregation and are supported by the computational apoE outcome. Additional computational work concerning the apoE\u2013\u0391\u03b2 complex also designates apoE amyloidogenic regions as important binding sites for oligomeric \u0391\u03b2; taking an important step forward in the field of Alzheimer\u2019s anti-aggregation drug development.<\/jats:p>","DOI":"10.3390\/ijms20092274","type":"journal-article","created":{"date-parts":[[2019,5,9]],"date-time":"2019-05-09T08:19:59Z","timestamp":1557389999000},"page":"2274","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Hidden Aggregation Hot-Spots on Human Apolipoprotein E: A Structural Study"],"prefix":"10.3390","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9525-6433","authenticated-orcid":false,"given":"Paraskevi L.","family":"Tsiolaki","sequence":"first","affiliation":[{"name":"Section of Cell Biology and Biophysics, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15701, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aikaterini D.","family":"Katsafana","sequence":"additional","affiliation":[{"name":"Section of Cell Biology and Biophysics, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15701, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2870-2931","authenticated-orcid":false,"given":"Fotis A.","family":"Baltoumas","sequence":"additional","affiliation":[{"name":"Section of Cell Biology and Biophysics, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15701, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4030-1022","authenticated-orcid":false,"given":"Nikolaos N.","family":"Louros","sequence":"additional","affiliation":[{"name":"Section of Cell Biology and Biophysics, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15701, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9472-5146","authenticated-orcid":false,"given":"Vassiliki A.","family":"Iconomidou","sequence":"additional","affiliation":[{"name":"Section of Cell Biology and Biophysics, Department of Biology, National and Kapodistrian University of Athens, Panepistimiopolis, Athens 15701, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4171","DOI":"10.1016\/S0021-9258(18)34702-1","article-title":"Human apolipoprotein E. 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