{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T03:38:14Z","timestamp":1785209894642,"version":"3.55.0"},"reference-count":70,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,1,3]],"date-time":"2025-01-03T00:00:00Z","timestamp":1735862400000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["NSTC 111\u20102320\u2010B\u2010003\u2010008"],"award-info":[{"award-number":["NSTC 111\u20102320\u2010B\u2010003\u2010008"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100012553","name":"Chang Gung Memorial Hospital","doi-asserted-by":"publisher","award":["CMRPG3L0042"],"award-info":[{"award-number":["CMRPG3L0042"]}],"id":[{"id":"10.13039\/100012553","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Misfolding and accumulation of amyloid\u2010\u03b2 (A\u03b2) in the brains of patients with Alzheimer's disease (AD) lead to neuronal loss through various mechanisms, including the downregulation of eukaryotic elongation factor 2 (EEF2) protein synthesis signaling. This study investigated the neuroprotective effects of indole and coumarin derivatives on A\u03b2 folding and EEF2 signaling using SH\u2010SY5Y cells expressing A\u03b2\u2010green fluorescent protein (GFP) folding reporter. Among the tested compounds, two indole (NC009\u20101, \u20106) and two coumarin (LM\u2010021, \u2010036) derivatives effectively reduced A\u03b2 misfolding and associated reactive oxygen species (ROS) production. Additionally, these compounds decreased acetylcholinesterase and caspase\u20103\/\u20106 activities while promoting neurite outgrowth. NC009\u20101 increased active phosphorylation of extracellular\u2010signal regulated kinase (ERK) (T202\/Y204), leading to an increase in inactive eukaryotic elongation factor 2 kinase (EEF2K) phosphorylation (S366). LM\u2010021 decreased the active phosphorylation of AMP\u2010activated protein kinase (AMPK) (T172) and EEF2K (S398), while LM\u2010036 exhibited dual effects, increasing inactive phosphorylation and decreasing active phosphorylation of EEF2K. These changes in EEF2K phosphorylation led to decreased EEF2K activity and a subsequent reduction in inactive phosphorylation of EEF2 (T56). This cascade further promoted the phosphorylation of transcription factor cAMP\u2010response\u2010element binding protein (CREB) (S133) and the expression of brain\u2010derived neurotrophic factor (BDNF), and reduced BCL\u20102 associated X\u2010protein (BAX)\/B\u2010cell lymphoma 2 (BCL2) ratio. Knockdown of EEF2 abolished the effects of NC009\u20101, LM\u2010021, and LM\u2010036 on CREB phosphorylation, BDNF expression, caspase\u20103 activity, and neurite outgrowth. These findings demonstrate that NC009\u20101, LM\u2010021, and LM\u2010036 exert their neuroprotective effects through modulation of EEF2K signaling, highlighting their potentials as therapeutic candidates for AD.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc16300-fig-0007-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1111\/jnc.16300","type":"journal-article","created":{"date-parts":[[2025,1,4]],"date-time":"2025-01-04T02:25:08Z","timestamp":1735957508000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Indole and Coumarin Derivatives Targeting\n                    <scp>EEF2K<\/scp>\n                    in A\u03b2 Folding Reporter Cells"],"prefix":"10.1111","volume":"169","author":[{"given":"Shun\u2010Tzu","family":"Chi","sequence":"first","affiliation":[{"name":"School of Life Science National Taiwan Normal University  Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Cih","family":"Wei","sequence":"additional","affiliation":[{"name":"Department of Neurology Chang Gung Memorial Hospital, Chang Gung University College of Medicine  Taoyuan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya\u2010Jen","family":"Chiu","sequence":"additional","affiliation":[{"name":"School of Life Science National Taiwan Normal University  Taipei 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