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However, the structure and consequences of the formation of these complexes remains to be determined. The main objective of this study was to characterise the different types and morphology of A\u03b2-hIAPP heterocomplexes and determine if formation of such complexes exacerbate neurotoxicity. We demonstrate that hIAPP promotes A\u03b2 oligomerization and formation of small oligomer and large aggregate heterocomplexes. Co-oligomerized A\u03b242-hIAPP mixtures displayed distinct amorphous structures and a 3-fold increase in neuronal cell death as compared to A\u03b2 and hIAPP alone. However, in contrast to hIAPP, non-amyloidogenic rat amylin (rIAPP) reduced oligomer A\u03b2-mediated neuronal cell death. rIAPP exhibited reductions in A\u03b2 induced neuronal cell death that was independent of its ability to interact with A\u03b2 and form heterocomplexes; suggesting mediation by other pathways. Our findings reveal distinct effects of IAPP peptides in modulating A\u03b2 aggregation and toxicity and provide new insight into the potential pathogenic effects of A\u03b2-IAPP hetero-oligomerization and development of IAPP based therapies for AD and T2D.<\/jats:p>","DOI":"10.1038\/s41598-020-66602-9","type":"journal-article","created":{"date-parts":[[2020,6,25]],"date-time":"2020-06-25T10:03:02Z","timestamp":1593079382000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Amylin and beta amyloid proteins interact to form amorphous heterocomplexes with enhanced toxicity in neuronal cells"],"prefix":"10.1038","volume":"10","author":[{"given":"Prashant","family":"Bharadwaj","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7762-9809","authenticated-orcid":false,"given":"Tanya","family":"Solomon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bikash R.","family":"Sahoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7742-4619","authenticated-orcid":false,"given":"Katarzyna","family":"Ignasiak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Gaskin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joanne","family":"Rowles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Verdile","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0762-2887","authenticated-orcid":false,"given":"Mark J.","family":"Howard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9584-6783","authenticated-orcid":false,"given":"Charles S.","family":"Bond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayyalusamy","family":"Ramamoorthy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralph N.","family":"Martins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philip","family":"Newsholme","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,6,25]]},"reference":[{"key":"66602_CR1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11892-014-0487-z","volume":"14","author":"T Ninomiya","year":"2014","unstructured":"Ninomiya, T. 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