{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T04:01:39Z","timestamp":1780286499949,"version":"3.54.0"},"reference-count":59,"publisher":"Wiley","issue":"12","license":[{"start":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T00:00:00Z","timestamp":1766102400000},"content-version":"vor","delay-in-days":18,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R25\u2010GM07763410"],"award-info":[{"award-number":["R25\u2010GM07763410"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["T34\u2010GM149434\u201001A1"],"award-info":[{"award-number":["T34\u2010GM149434\u201001A1"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG072958"],"award-info":[{"award-number":["P30AG072958"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["alz-journals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Alzheimer's &amp;amp; Dementia"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>INTRODUCTION<\/jats:title>\n                    <jats:p>Disruption of the autophagy\u2010lysosomal pathway (ALP) compromises proteostasis and contributes to aging\u2010related proteinopathy. Many studies indicate that a healthy diet can improve cognitive health and reduce the risk of Alzheimer\u2010type pathogenesis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>\n                      Plant\u2010based products were tested in hippocampal explants for amplifying the ALP component cathepsin B (CatB), a protease reported to reduce proteinopathy and synaptopathy. Proof\u2010of\u2010concept experiments also tested\n                      <jats:italic>Panax quinquefolius<\/jats:italic>\n                      extract (PanQ) for improving cognitive function in aging rats.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>Among the natural extracts tested, PanQ emerged as the most effective for increasing the active CatB isoform in correspondence with enhanced levels of synaptic proteins and the autophagy marker LC3\u2010II. PanQ also increased synaptic resilience in a model of lysosomal stress and improved cognitive performance in 20\u2010month\u2010old rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>DISCUSSION<\/jats:title>\n                    <jats:p>PanQ\u2010mediated ALP enhancement implicates the proteostasis network in synaptic and cognitive maintenance mechanisms. This study also points to synaptic resiliency as an important factor underlying the influence of dietary components on cognitive health.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Highlights<\/jats:title>\n                    <jats:p>\n                      <jats:list list-type=\"bullet\">\n                        <jats:list-item>\n                          <jats:p>\n                            <jats:italic>Panax quinquefolius<\/jats:italic>\n                            (PanQ) enhanced cathepsin B (CatB) in hippocampal explants.\n                          <\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>The CatB modulation corresponded with enhanced synaptic and autophagy markers.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>PanQ improved synaptic resilience in the chloroquine (Cqn) model of lysosomal stress.<\/jats:p>\n                        <\/jats:list-item>\n                        <jats:list-item>\n                          <jats:p>Age\u2010related cognitive deficit was reduced by PanQ supplementation in Fischer rats.<\/jats:p>\n                        <\/jats:list-item>\n                      <\/jats:list>\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/alz.70818","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T12:00:16Z","timestamp":1766145616000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ginseng extract improves synaptic resiliency: A key factor for healthy cognitive aging"],"prefix":"10.1002","volume":"21","author":[{"given":"Michael F.","family":"Almeida","sequence":"first","affiliation":[{"name":"Biotechnology Research and Training Center University of North Carolina\u2010Pembroke Pembroke North Carolina USA"},{"name":"Department of Biology &amp; Marine Biology, and the Integrative, Comparative &amp; Marine Biology Program University of North Carolina\u2013Wilmington  Wilmington North Carolina USA"},{"name":"McAllister Heart Institute and the Department of Pharmacology University of North Carolina\u2013Chapel Hill  Chapel Hill North Carolina USA"},{"name":"The Duke &amp; University of North Carolina Alzheimer's Disease Research Center Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Morgan C.","family":"Pait","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Training Center University of North Carolina\u2010Pembroke Pembroke North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine M.","family":"Rentschler","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Training Center University of North Carolina\u2010Pembroke Pembroke North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Norton","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Training Center University of North Carolina\u2010Pembroke Pembroke North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karen L. G.","family":"Farizatto","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Training Center University of North Carolina\u2010Pembroke Pembroke North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben A.","family":"Bahr","sequence":"additional","affiliation":[{"name":"Biotechnology Research and Training Center University of North Carolina\u2010Pembroke Pembroke North Carolina USA"},{"name":"The Duke &amp; University of North Carolina Alzheimer's Disease Research Center Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.109.108266"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1079\/096582197388554"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.3945\/jn.109.106427"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1396.037"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd.2018.109"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2023.102162"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010021\u201000098\u20104"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.15252\/embj.2021108863"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2006.8.185"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2004.05.003"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.conb.2017.09.005"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41580\u2010024\u201000757\u20105"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471\u20104159.2002.01192.x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2016.04.005"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.irn.2020.02.012"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11064\u2010013\u20101129\u20106"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2010.05.014"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12263\u2010009\u20100136\u20103"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1039\/c0np00027b"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.07.027"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020501"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20184432"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2402117122"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.11\u2010182154"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1523\/jneurosci.1318\u201023.2023"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M112.371641"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2019.06.013"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010025\u201000886\u20101"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/62.5.451"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.2121609119"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.14286"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/bcp.12002"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/ptr.5682"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19020461"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010019\u201042934\u2010z"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.16864"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.70160"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0182895"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1021\/ml300197h"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/61.7.640"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2007.01.053"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neurobiolaging.2011.11.009"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11481\u2010016\u20109721\u20106"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1097\/nen.0b013e3181461ae7"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb3388"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0167428"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096\u20109861(19980720)397:1<139::AID\u2010CNE10>3.0.CO;2\u2010K"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010016\u20101577\u20106"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41556\u2010025\u201001623\u2010y"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201704068"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1523\/eneuro.0258\u201023.2023"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024\u2010023\u201000621\u20108"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.12.018"},{"key":"e_1_2_8_55_1","doi-asserted-by":"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