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While both amyloid cross\u2010seeding and amyloid inhibition are critical for better understanding the pathological causes of different neurodegenerative diseases including Parkinson disease (PD) and Type 2 diabetes (T2D), less efforts have been made to reconcile the two phenomena. Herein, we proposed a new preventive strategy to demonstrate (a) the cross\u2010seeding of octapeptide TKEQVTNV from \u03b1\u2010synuclein (associated with PD) with hIAPP (associated with T2D) and (b) the cross\u2010seeding\u2010promoted hIAPP fibrillization and cross\u2010seeding\u2010reduced hIAPP toxicity. Collective results confirmed that TKEQVTNV can indeed cross\u2010seed with hIAPP monomers and oligomers, not protofibrils, to form \u03b2\u2010structure\u2010rich fibrils and to accelerate hIAPP fibrillization. Moreover, such cross\u2010seeding\u2010induced promotion effect by TKEQVTNV also rescued the pancreatic cells from hIAPP\u2010induced cytotoxicity by increasing cell viability and reducing cell apoptosis simultaneously. This work provides a new angle to discover amyloid fragments and use them as amyloid modulators (inhibitors or promotors) to interfere with amyloid aggregation of other amyloid proteins, as well as sequence\/structure basis to explore the amyloid cross\u2010seeding between different amyloid proteins that may help explain a potential molecular talk between different neurodegenerative diseases.<\/jats:p>","DOI":"10.1002\/pro.4247","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T11:32:14Z","timestamp":1638358334000},"page":"485-497","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["A new strategy to reconcile amyloid cross\u2010seeding and amyloid prevention in a binary system of \u03b1\u2010synuclein fragmental peptide and <scp>hIAPP<\/scp>"],"prefix":"10.1002","volume":"31","author":[{"given":"Yijing","family":"Tang","sequence":"first","affiliation":[{"name":"Department of 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