{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T06:08:48Z","timestamp":1790489328130,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2011,5,31]],"date-time":"2011-05-31T00:00:00Z","timestamp":1306800000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2011,6,14]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Alzheimer's disease (AD) and type 2 diabetes (T2D) are linked to the self\u2010association of \u03b2\u2010amyloid peptide (A\u03b2) and islet amyloid polypeptide (IAPP), respectively. We have shown that IAPP\u2010GI, a soluble IAPP analogue and mimic of nonamyloidogenic and nontoxic IAPP, binds A\u03b2 with high affinity and blocks its cytotoxic self\u2010assembly and fibrillogenesis. We have also shown that IAPP and A\u03b2 interact with each other into nonfibrillar and nontoxic heterocomplexes that suppress cytotoxic self\u2010association by both polypeptides. The A\u03b2\u2013IAPP interaction might thus be a molecular link between AD and T2D. We studied the role of individual IAPP\u2010GI and IAPP regions in their inhibitory function on A\u03b240 self\u2010association and cytotoxicity. We found that the presence of the two hot\u2010spot regions of the A\u03b2\u2013IAPP interaction interface in IAPP(8\u201328) is not sufficient for inhibitory function and that, in addition to IAPP(8\u201328), the presence of the N\u2010terminal region IAPP(1\u20137) is absolutely required. By contrast, the C\u2010terminal region, IAPP(30\u201337), is not required although its presence together with IAPP(1\u20137) in IAPP\u2010GI results in a marked enhancement of the inhibitory effect as compared to IAPP(1\u201328)\u2010GI. We suggest that the inhibitory effect of IAPP\u2010GI and IAPP on A\u03b240 fibrillogenesis and cell toxicity is mediated primarily by interactions involving the hot regions of the A\u03b2\u2013IAPP interaction interface and the N terminus of IAPP while a concerted and likely structure\u2010stabilizing action of the N\u2010 and C\u2010terminal IAPP regions potentiates this effect. These results identify important molecular determinants of the amyloid suppressing function of the A\u03b240\u2013IAPP interaction and could contribute to the design of novel inhibitors of A\u03b240 aggregation and cell degeneration.<\/jats:p>","DOI":"10.1002\/cbic.201100192","type":"journal-article","created":{"date-parts":[[2011,5,31]],"date-time":"2011-05-31T11:33:58Z","timestamp":1306841638000},"page":"1313-1322","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Dissecting the Role of Single Regions of an IAPP Mimic and IAPP in Inhibition of A\u03b240 Amyloid Formation and Cytotoxicity"],"prefix":"10.1002","volume":"12","author":[{"given":"Erika","family":"Andreetto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li\u2010Mei","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Caporale","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aphrodite","family":"Kapurniotu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2011,5,31]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1742-4658.2005.05024.x"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.2174\/092986606775338362"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.2174\/1567205043480555"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresrev.2007.09.001"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2010.130"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M311300200"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200604056"},{"key":"e_1_2_6_7_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200604056"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2008.08.019"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200904902"},{"key":"e_1_2_6_9_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200904902"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0282(2001)60:6<438::AID-BIP10182>3.0.CO;2-A"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0507471103"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2125.2010.03830.x"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja1046186"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0076-6879(99)09020-5"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2005.05.010"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.4.1470"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1995.65010218.x"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.92.6.1989"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200801499"},{"key":"e_1_2_6_19_3","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200801499"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.4593"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(00)00034-X"},{"key":"e_1_2_6_22_2","first-page":"221","volume-title":"Methods in Enzymology: Fluorescence Spectroscopy, Vol. 278","author":"Eftink M. R.","year":"1997"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1002\/pro.145"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.200900237"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.1999.2646"},{"key":"e_1_2_6_26_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M100252200"},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1006\/jsbi.2000.4268"},{"key":"e_1_2_6_28_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(02)00887-2"},{"key":"e_1_2_6_29_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.0014-2956.2001.02689.x"}],"container-title":["ChemBioChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcbic.201100192","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbic.201100192","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T20:18:41Z","timestamp":1760300321000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cbic.201100192"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,5,31]]},"references-count":32,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2011,6,14]]}},"alternative-id":["10.1002\/cbic.201100192"],"URL":"https:\/\/doi.org\/10.1002\/cbic.201100192","archive":["Portico"],"relation":{},"ISSN":["1439-4227","1439-7633"],"issn-type":[{"value":"1439-4227","type":"print"},{"value":"1439-7633","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,5,31]]},"assertion":[{"value":"2011-03-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2011-05-31","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}