{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T15:30:48Z","timestamp":1778686248480,"version":"3.51.4"},"reference-count":42,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2017,5,25]],"date-time":"2017-05-25T00:00:00Z","timestamp":1495670400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2017,6,23]]},"abstract":"<jats:p>\n                    Apomorphine (APO) promotes intraneuronal amyloid-\u03b2 (A\u03b2) degradation and improves memory function in an Alzheimer\u2019s disease (AD) model, 3xTg-AD mice. Since insulin resistance is increased in AD neurons, we investigated the effects of APO on brain insulin resistance in 3xTg-AD mice at early and late stages. After 1-month subcutaneous injection of Apokyn\n                    <jats:sup>\u00ae<\/jats:sup>\n                    to 3xTg-AD mice at 6 or 12 months of age, memory function was significantly improved in both age groups. Protein levels of insulin-degrading enzyme (IDE), which is linked to insulin signaling and degrades A\u03b2, significantly increased in the 3xTg-AD mice brain compared with non-transgenic mice, and were further increased by APO. Protein levels of two types of serine-phosphorylated insulin receptor substrate-1 (IRS-1), pS\n                    <jats:sup>616<\/jats:sup>\n                    and pS\n                    <jats:sup>636\/639<\/jats:sup>\n                    , significantly decreased following APO treatment in the 13-month-old 3xTg-AD mice brain, suggesting improved brain insulin resistance. Immunostaining of the IDE, pS\n                    <jats:sup>616<\/jats:sup>\n                    and pS\n                    <jats:sup>636\/639<\/jats:sup>\n                    IRS-1 demonstrated similar changes due to APO treatment. Thus, brain insulin resistance is considered an important therapeutic target in AD, and APO may provide improved neuronal insulin resistance.\n                  <\/jats:p>","DOI":"10.3233\/jad-160344","type":"journal-article","created":{"date-parts":[[2017,5,26]],"date-time":"2017-05-26T14:46:05Z","timestamp":1495809965000},"page":"1151-1161","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":25,"title":["Apomorphine Therapy for Neuronal Insulin Resistance in a Mouse Model of Alzheimer\u2019s Disease"],"prefix":"10.1177","volume":"58","author":[{"given":"Norimichi","family":"Nakamura","sequence":"first","affiliation":[{"name":"Department of Neurology, Neurological Institute, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yasumasa","family":"Ohyagi","sequence":"additional","affiliation":[{"name":"Department of Geriatric Medicine and 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