{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T07:27:40Z","timestamp":1779089260139,"version":"3.51.4"},"reference-count":30,"publisher":"Elsevier BV","issue":"7","license":[{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2022,7,1]],"date-time":"2022-07-01T00:00:00Z","timestamp":1656633600000},"content-version":"vor","delay-in-days":365,"URL":"http:\/\/www.elsevier.com\/open-access\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,7,1]],"date-time":"2021-07-01T00:00:00Z","timestamp":1625097600000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100002283","name":"Alzheimer\u2019s Research UK","doi-asserted-by":"publisher","award":["ARUK-PG2017B-11"],"award-info":[{"award-number":["ARUK-PG2017B-11"]}],"id":[{"id":"10.13039\/501100002283","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000882","name":"University of Aberdeen","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000882","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"],"published-print":{"date-parts":[[2021,7]]},"DOI":"10.1016\/j.bbadis.2021.166149","type":"journal-article","created":{"date-parts":[[2021,4,20]],"date-time":"2021-04-20T15:26:18Z","timestamp":1618932378000},"page":"166149","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":18,"title":["The BACE1 inhibitor LY2886721 improves diabetic phenotypes of BACE1 knock-in mice"],"prefix":"10.1016","volume":"1867","author":[{"given":"Ruta","family":"Dekeryte","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zara","family":"Franklin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claire","family":"Hull","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorenzo","family":"Croce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Kamli-Salino","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Helk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip A.","family":"Hoffmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhixiang","family":"Yang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gernot","family":"Riedel","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mirela","family":"Delibegovic","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bettina","family":"Platt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"78","reference":[{"key":"10.1016\/j.bbadis.2021.166149_bb0005","doi-asserted-by":"crossref","DOI":"10.2147\/CIA.S74042","article-title":"Link between type 2 diabetes and Alzheimer\u2019s disease: from epidemiology to mechanism and treatment","author":"Li","year":"2015","journal-title":"Clin. Interv. Aging"},{"key":"10.1016\/j.bbadis.2021.166149_bb0010","doi-asserted-by":"crossref","DOI":"10.3389\/fnins.2018.00383","article-title":"Alzheimer\u2019s disease and type 2 diabetes: a critical assessment of the shared pathological traits","volume":"12","author":"Chatterjee","year":"2018","journal-title":"Front. Neurosci."},{"key":"10.1016\/j.bbadis.2021.166149_bb0015","doi-asserted-by":"crossref","DOI":"10.1016\/j.neuropharm.2018.01.008","article-title":"Evidence for altered insulin receptor signaling in Alzheimer\u2019s disease","author":"Griffith","year":"2018","journal-title":"Neuropharmacology"},{"key":"10.1016\/j.bbadis.2021.166149_bb0020","doi-asserted-by":"crossref","DOI":"10.3233\/JAD-130005","article-title":"Type 2 diabetic and alzheimer\u2019s disease mice present similar behavioral, cognitive, and vascular anomalies","author":"Carvalho","year":"2013","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.bbadis.2021.166149_bb0025","article-title":"The \u03b2-secretase BACE1 in Alzheimer\u2019s disease","author":"Hampel","year":"2020","journal-title":"Biol. Psychiatry"},{"key":"10.1016\/j.bbadis.2021.166149_bb0030","doi-asserted-by":"crossref","DOI":"10.3389\/fchem.2018.00178","article-title":"Highlights in BACE1 inhibitors for Alzheimer\u2019s disease treatment","author":"Coimbra","year":"2018","journal-title":"Front. Chem."},{"key":"10.1016\/j.bbadis.2021.166149_bb0035","doi-asserted-by":"crossref","DOI":"10.1007\/s40263-019-00613-7","article-title":"A close look at BACE1 inhibitors for Alzheimer\u2019s disease treatment","author":"Das","year":"2019","journal-title":"CNS Drugs"},{"key":"10.1016\/j.bbadis.2021.166149_bb0040","doi-asserted-by":"crossref","DOI":"10.1042\/BJ20110512","article-title":"Reduction in BACE1 decreases body weight, protects against diet-induced obesity and enhances insulin sensitivity in mice","author":"Meakin","year":"2012","journal-title":"Biochem. J."},{"key":"10.1016\/j.bbadis.2021.166149_bb0045","doi-asserted-by":"crossref","DOI":"10.1007\/s00125-016-3960-1","article-title":"Neuronal human BACE1 knockin induces systemic diabetes in mice","author":"Pluci\u0144ska","year":"2016","journal-title":"Diabetologia"},{"key":"10.1016\/j.bbadis.2021.166149_bb0050","doi-asserted-by":"crossref","DOI":"10.1038\/s41467-018-03755-2","article-title":"The beta secretase BACE1 regulates the expression of insulin receptor in the liver","author":"Meakin","year":"2018","journal-title":"Nat. Commun."},{"key":"10.1016\/j.bbadis.2021.166149_bb0055","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2019.05.020","article-title":"Effects of Liraglutide and Fenretinide treatments on the diabetic phenotype of neuronal human BACE1 knock-in mice","author":"Dekeryte","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.bbadis.2021.166149_bb0060","doi-asserted-by":"crossref","DOI":"10.1038\/s41598-017-18388-6","article-title":"Bace1-dependent amyloid processing regulates hypothalamic leptin sensitivity in obese mice","author":"Meakin","year":"2018","journal-title":"Sci. Rep."},{"key":"10.1016\/j.bbadis.2021.166149_bb0065","doi-asserted-by":"crossref","DOI":"10.1523\/JNEUROSCI.4129-14.2015","article-title":"The potent BACE1 inhibitor LY2886721 elicits robust central A\u03b2 pharmacodynamic responses in mice, dogs, and humans","author":"May","year":"2015","journal-title":"J. Neurosci."},{"key":"10.1016\/j.bbadis.2021.166149_bb0070","doi-asserted-by":"crossref","DOI":"10.1021\/op500327t","article-title":"Synthesis of BACE inhibitor LY2886721. Part II. Isoxazolidines as precursors to chiral aminothiazines, selective peptide coupling, and a controlled reactive crystallization","author":"Hansen","year":"2015","journal-title":"Org. Process. Res. Dev."},{"key":"10.1016\/j.bbadis.2021.166149_bb0075","doi-asserted-by":"crossref","DOI":"10.1523\/JNEUROSCI.3647-11.2011","article-title":"Robust central reduction of amyloid-\u03b2 in humans with an orally available, non-peptidic \u03b2-secretase inhibitor","author":"May","year":"2011","journal-title":"J. Neurosci."},{"key":"10.1016\/j.bbadis.2021.166149_bb0080","series-title":"Developing Therapeutics for Alzheimer\u2019s Disease","article-title":"Prospects and challenges for alzheimer therapeutics","author":"Wolfe","year":"2016"},{"key":"10.1016\/j.bbadis.2021.166149_bb0085","doi-asserted-by":"crossref","DOI":"10.1016\/j.jalz.2013.11.004","article-title":"Lessons from a BACE1 inhibitor trial: off-site but not off base","author":"Lahiri","year":"2014","journal-title":"Alzheimers Dement."},{"key":"10.1016\/j.bbadis.2021.166149_bb0090","doi-asserted-by":"crossref","DOI":"10.1523\/JNEUROSCI.0433-14.2014","article-title":"Knock-in of human BACE1 cleaves murine APP and reiterates alzheimer-like phenotypes","author":"Pluci\u0144ska","year":"2014","journal-title":"J. Neurosci."},{"key":"10.1016\/j.bbadis.2021.166149_bb0095","doi-asserted-by":"crossref","DOI":"10.1007\/s12035-019-01722-6","article-title":"Knock-in of mutated hTAU causes insulin resistance, inflammation and proteostasis disturbance in a mouse model of frontotemporal dementia","author":"Hull","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.bbadis.2021.166149_bb0100","doi-asserted-by":"crossref","DOI":"10.1186\/s40035-016-0061-5","article-title":"Stepping closer to treating Alzheimer\u2019s disease patients with BACE1 inhibitor drugs","volume":"5","author":"Yan","year":"2016","journal-title":"Transl. Neurodegener."},{"key":"10.1016\/j.bbadis.2021.166149_bb0105","doi-asserted-by":"crossref","DOI":"10.1074\/jbc.M002688200","article-title":"Expression analysis of BACE2 in brain and peripheral tissues","author":"Bennett","year":"2000","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bbadis.2021.166149_bb0110","doi-asserted-by":"crossref","DOI":"10.1016\/j.cmet.2011.06.018","article-title":"Bace2 is a \u03b2 cell-enriched protease that regulates pancreatic \u03b2 cell function and mass","author":"Esterh\u00e1zy","year":"2011","journal-title":"Cell Metab."},{"key":"10.1016\/j.bbadis.2021.166149_bb0115","doi-asserted-by":"crossref","DOI":"10.1007\/s00018-017-2505-1","article-title":"BACE2 suppression promotes \u03b2-cell survival and function in a model of type 2 diabetes induced by human islet amyloid polypeptide overexpression","author":"Alcarraz-Viz\u00e1n","year":"2017","journal-title":"Cell. Mol. Life Sci."},{"key":"10.1016\/j.bbadis.2021.166149_bb0120","article-title":"High-fat diet exacerbates cognitive and metabolic abnormalities in neuronal BACE1 knock-in mice\u2013partial prevention by Fenretinide","author":"Pluci\u0144ska","year":"2020","journal-title":"Nutr. Neurosci."},{"key":"10.1016\/j.bbadis.2021.166149_bb0125","doi-asserted-by":"crossref","DOI":"10.3233\/JAD-170581","article-title":"The unexpected role of A\u03b2 1-42 monomers in the pathogenesis of Alzheimer\u2019s disease","author":"Tamagno","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"10.1016\/j.bbadis.2021.166149_bb0130","doi-asserted-by":"crossref","DOI":"10.1111\/j.1471-4159.2006.04178.x","article-title":"BACE1 inhibition reduces endogenous Abeta and alters APP processing in wild-type mice2","author":"Nishitomi","year":"2006","journal-title":"J. Neurochem."},{"key":"10.1016\/j.bbadis.2021.166149_bb0135","article-title":"Bace 1","author":"Vassar","year":"2004","journal-title":"J. Mol. Neurosci."},{"key":"10.1016\/j.bbadis.2021.166149_bb0140","doi-asserted-by":"crossref","DOI":"10.1523\/JNEUROSCI.2766-05.2005","article-title":"BACE1, a major determinant of selective vulnerability of the brain to amyloid-\u03b2 amyloidogenesis, is essential for cognitive, emotional, and synaptic functions","author":"Laird","year":"2005","journal-title":"J. Neurosci."},{"key":"10.1016\/j.bbadis.2021.166149_bb0145","doi-asserted-by":"crossref","DOI":"10.1074\/jbc.M611687200","article-title":"Partial reduction of BACE1 has dramatic effects on Alzheimer plaque and synaptic pathology in APP transgenic mice","author":"McConlogue","year":"2007","journal-title":"J. Biol. Chem."},{"key":"10.1016\/j.bbadis.2021.166149_bb0150","doi-asserted-by":"crossref","DOI":"10.1080\/13543784.2019.1683160","article-title":"Investigational BACE inhibitors for the treatment of Alzheimer\u2019s disease","author":"Imbimbo","year":"2019","journal-title":"Expert Opin. Investig. Drugs"}],"container-title":["Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S092544392100082X?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S092544392100082X?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T05:03:59Z","timestamp":1760418239000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S092544392100082X"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7]]},"references-count":30,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2021,7]]}},"alternative-id":["S092544392100082X"],"URL":"https:\/\/doi.org\/10.1016\/j.bbadis.2021.166149","relation":{},"ISSN":["0925-4439"],"issn-type":[{"value":"0925-4439","type":"print"}],"subject":[],"published":{"date-parts":[[2021,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"The BACE1 inhibitor LY2886721 improves diabetic phenotypes of BACE1 knock-in mice","name":"articletitle","label":"Article Title"},{"value":"Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bbadis.2021.166149","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier B.V.","name":"copyright","label":"Copyright"}],"article-number":"166149"}}