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We have previously shown that amylin receptor antagonist, AC253, improves spatial memory in AD mouse models. Herein, we generated and screened a peptide library and identified two short sequence amylin peptides (12\u201314 aa) that are proteolytically stable, brain penetrant when administered intraperitoneally, neuroprotective against A\u03b2 toxicity and restore diminished levels of hippocampal long term potentiation in AD mice. Systemic administration of the peptides for five weeks in aged 5XFAD mice improved spatial memory, reduced amyloid plaque burden, and neuroinflammation. The common residue SQELHRLQTY within the peptides is an essential sequence for preservation of the beneficial effects of the fragments that we report here and constitutes a new pharmacological target. These findings suggest that the amylin receptor antagonism may represent a novel therapy for AD.<\/jats:p>","DOI":"10.1038\/s41598-019-47255-9","type":"journal-article","created":{"date-parts":[[2019,7,29]],"date-time":"2019-07-29T10:21:36Z","timestamp":1564395696000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":35,"title":["Short amylin receptor antagonist peptides improve memory deficits in Alzheimer\u2019s disease mouse model"],"prefix":"10.1038","volume":"9","author":[{"given":"Rania","family":"Soudy","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryoichi","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aarti","family":"Patel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wen","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamaljit","family":"Kaur","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1928-4616","authenticated-orcid":false,"given":"David","family":"Westaway","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack","family":"Jhamandas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,7,29]]},"reference":[{"key":"47255_CR1","unstructured":"Alzheimer\u2019s.net. 2017 Alzheimer\u2019s Statistics. http:\/\/www.alzheimers.net\/resources\/alzheimers-statistics\/ Accessed January 28, 2019."},{"key":"47255_CR2","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1126\/science.1072994","volume":"297","author":"J Hardy","year":"2002","unstructured":"Hardy, J. & Selkoe, D. 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Inventors are: Jhamandas, Jack; Soudy, Rania; Kaur, Kamaljit; Fu, Wen; MacTavish, David and Patel, Aarti. Title: Brain Penetrant Amylin Receptor Based Peptides for Alzheimer\u2019s Disease. The patent relates to the generation and application of short amylin receptor antagonist peptides that are used in the studies described in this manuscript.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"10942"}}