{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T01:48:27Z","timestamp":1781574507180,"version":"3.54.5"},"reference-count":46,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82260842"],"award-info":[{"award-number":["82260842"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100018555","name":"Science and Technology Program of Guizhou Province","doi-asserted-by":"publisher","award":["[2020]1Z075"],"award-info":[{"award-number":["[2020]1Z075"]}],"id":[{"id":"10.13039\/501100018555","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Alzheimer's disease (AD) is a progressive neurodegenerative disorder with cognitive impairment that currently is incurable. There is existing evidence to suggest that vacuolar adenosine triphosphatase (v\u2010ATPase) is one of the early key driving factors in the pathological process of AD. Thus, early intervention of v\u2010ATPase may be a viable strategy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>Observing whether early intervention with DNLA can delay learning and memory impairment in mice, and further exploring the mechanism of DNLA delaying AD in\u00a0vitro based on v\u2010ATPase.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Four\u2010month\u2010old APP\/PS1 transgenic mice were treated with alkaloids from Dendrobium nobile Lindl (DNLA) 20 and 40\u2009mg\/kg\/day for 5\u2009months. The Morris water maze test and nest test showed that DNLA administration significantly delayed the appearance of cognitive deficits in APP\/PS1 mice. We further investigated the mechanism of DNLA promoting lysosome acidification in\u00a0vitro by using PC12 cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that DNLA increases the degradation of \u03b2\u2010amyloid (A\u03b2) contained in the autophagic lysosomes and alleviates the aging of neurons by promoting lysosome acidification and improving autophagy flow. In PC12 cells, DDB could promote the separation of mTOR and lysosome, promote the nuclear translocation of transcription factor EB (TFEB), and then promote lysosome biogenesis and lysosome acidification by targeting ATP6V1A.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These results unraveled that preventive administration of DNLA may delay the impairment of learning and memory in APP\/PS1 mice. The molecular mechanism may be related to promoting the mTOR\u2010TFEB\u2010v\u2010ATPase pathway.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cns.70300","type":"journal-article","created":{"date-parts":[[2025,3,12]],"date-time":"2025-03-12T05:59:05Z","timestamp":1741759145000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>DNLA<\/scp> Delayed the Appearance of Learning and Memory Impairment of <scp>APP<\/scp>\/<scp>PS1<\/scp> Mice: Involvement of <scp>mTOR<\/scp>\/<scp>TFEB<\/scp>\/v\u2010<scp>ATPase<\/scp> Signaling Pathway"],"prefix":"10.1111","volume":"31","author":[{"given":"Yajuan","family":"Wu","sequence":"first","affiliation":[{"name":"Key Laboratory of Basic Pharmacology of Ministry of Education Zunyi Medical University  Zunyi 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