{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T16:43:10Z","timestamp":1777394590379,"version":"3.51.4"},"reference-count":60,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2017,4,28]],"date-time":"2017-04-28T00:00:00Z","timestamp":1493337600000},"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":[[2017,5,11]]},"abstract":"<jats:p>\n                    Background: Metal-ion-chelation was suggested to prevent zinc and copper ions-induced amyloid-\u03b2 (A\u03b2) aggregation and oxidative stress, both implicated in the pathophysiology of Alzheimer\u2019s disease (AD). In a quest for biocompatible metal-ion chelators potentially useful for AD therapy, we previously tested a series of nucleoside 5\u2019-phosphorothioate derivatives as agents for decomposition of Cu(I)\/Cu(II)\/Zn(II)-A\u03b2-aggregates, and as inhibitors of OH radicals formation in Cu(I) or Fe(II) \/H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    solution. Specifically, in our recent study we have identified 2-SMe-ADP(\u03b1-S), designated as SAS, as a most promising neuroprotectant.\n                  <\/jats:p>\n                  <jats:p>Objective: To further explore SAS ability to protect the brain from A\u03b2 toxicity both in vitro and in vivo.<\/jats:p>\n                  <jats:p>\n                    Methods: We evaluated SAS ability to decompose or inhibit the formation of A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    -M(II) aggregates, and rescue primary neurons and astrocytes from A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    toxicity. Furthermore, we aimed at exploring the therapeutic effect of SAS on behavioral and cognitive deficits in the 5XFAD mouse model of AD.\n                  <\/jats:p>\n                  <jats:p>\n                    Results: We found that SAS can rescue primary culture of neurons and astrocytes from A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    toxicity and to inhibit the formation and dissolve A\u03b2\n                    <jats:sub>42<\/jats:sub>\n                    -Zn(II)\/Cu(II) aggregates. Furthermore, we show that SAS treatment can prevent behavioral disinhibition and ameliorate spatial working memory deficits in 5XFAD mice. Notably, the mice were treated at the age of 2 months, before the onset of AD symptoms, for a duration of 2 months, while the effect was demonstrated at the age of 6 months.\n                  <\/jats:p>\n                  <jats:p>Conclusion: Our results indicate that SAS has the potential to delay progression of core pathological characteristics of AD in the 5XFAD mouse model.<\/jats:p>","DOI":"10.3233\/jad-161236","type":"journal-article","created":{"date-parts":[[2017,4,28]],"date-time":"2017-04-28T12:12:49Z","timestamp":1493381569000},"page":"389-400","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["A Multifunctional Biocompatible Drug Candidate is Highly Effective in Delaying Pathological Signs of Alzheimer\u2019s Disease in 5XFAD Mice"],"prefix":"10.1177","volume":"58","author":[{"given":"Hadar","family":"Segal-Gavish","sequence":"first","affiliation":[{"name":"Laboratory of Neuroscience, 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