{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,14]],"date-time":"2025-10-14T00:30:18Z","timestamp":1760401818404,"version":"build-2065373602"},"reference-count":42,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Palmatine (PAL), as an active ingredient in traditional Chinese medicine, had been demonstrated efficacy in ameliorating the manifestations of AD. Our research group has previously designed and synthesized the novel oxo\u2010PAL derivative <jats:bold>2q<\/jats:bold> and found that it has exhibited notable neuroprotective properties. However, compound <jats:bold>2q<\/jats:bold> therapeutic impact on AD remains uncertain. In the current investigation, our findings demonstrated that compound <jats:bold>2q<\/jats:bold> displayed significant anti\u2010A\u03b2Os activity in vitro by using xCELLigence analysis, and showed a high likelihood of crossing the blood\u2010brain barrier. Furthermore, administration of compound <jats:bold>2q<\/jats:bold> yielded a notable amelioration in A\u03b2 accumulation and hyperphosphorylation of Tau in 3\u00d7Tg mice. Additionally, it was observed that compound <jats:bold>2q<\/jats:bold> potentially enhanced the pathological characteristics of AD by targeting Potassium\/Sodium Hyperpolarization\u2010Activated Cyclic Nucleotide\u2010Gated Channel 2 (HCN2). In conclusion, compound <jats:bold>2q<\/jats:bold> emerged as a promising candidate for AD treatment, as it effectively restored AD\u2010associated pathological impairments. Furthermore, it has been identified as a potential target of HCN2, thereby offering novel avenues for the development of treatments for AD.<\/jats:p>","DOI":"10.1002\/ddr.70073","type":"journal-article","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T06:15:56Z","timestamp":1741846556000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["A Novel Oxo\u2010Palmatine Derivative 2q as Potent Reversal Agents Against Alzheimer's Disease"],"prefix":"10.1002","volume":"86","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3753-1705","authenticated-orcid":false,"given":"Shuo","family":"Pang","sequence":"first","affiliation":[{"name":"The Laboratory of Neurological Disorders and Brain Cognition, Beijing Pediatric Research Institute, Beijing Children's Hospital, National Center for Children's Health Capital Medical University Beijing China"},{"name":"Laboratory for Clinical Medicine Capital Medical University 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