{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,30]],"date-time":"2026-06-30T09:45:29Z","timestamp":1782812729202,"version":"3.54.5"},"reference-count":49,"publisher":"SAGE Publications","issue":"1","license":[{"start":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T00:00:00Z","timestamp":1779667200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"funder":[{"DOI":"10.13039\/501100002649","name":"Yeungnam University","doi-asserted-by":"publisher","award":["2025 RISE Program"],"award-info":[{"award-number":["2025 RISE Program"]}],"id":[{"id":"10.13039\/501100002649","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Alzheimer\u2019s Disease"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Alzheimer's disease (AD) is a neurodegenerative disorder and the most common cause of dementia. The integrated stress response (ISR) contributes to impaired synaptic plasticity, neuronal dysfunction, and cognitive deficits in AD. However, research targeting the ISR as a therapeutic strategy for AD remains limited due to insufficient mechanistic insight.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aimed to evaluate the effects of 2BAct, an ISR inhibitor, on behavioral symptoms, amyloid-\u03b2 (A\u03b2) and tau accumulation, and neuroinflammation in 5xFAD mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Ten-month-old 5xFAD mice received daily intraperitoneal (IP) injections of either 2BAct (10\u2005mg\/kg\/day), donepezil (2\u2005mg\/kg\/day; positive control), or vehicle for 23 consecutive days. Anxiety-like behavior and cognitive function were assessed using the open field test (OFT), novel object recognition test (NORT), and Morris water maze (MWM). Amyloid-\u03b2 (A\u03b2), tau, and neuroinflammation markers were analyzed by immunofluorescence staining. ISR inhibition was evaluated by examining the phosphorylation level of eukaryotic initiation factor 2 alpha (eIF2\u03b1) using immunofluorescence staining and by analyzing ISR-related markers via RNA sequencing.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>2BAct treatment significantly improved object recognition performance and attenuated microglial activation and tau accumulation, without reducing A\u03b2 burden. Reduced levels of phosphorylated eIF2\u03b1 were also confirmed by immunofluorescence staining.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings suggest that 2BAct treatment improves cognitive performance and mitigates neuroinflammation while reducing tau accumulation. Although the therapeutic effects are limited, targeting the ISR with inhibitors such as 2BAct represents a potential therapeutic approach for AD. Further studies are required to elucidate the underlying molecular mechanisms and to address the limitations of ISR-based interventions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/13872877261450638","type":"journal-article","created":{"date-parts":[[2026,5,25]],"date-time":"2026-05-25T08:50:38Z","timestamp":1779699038000},"page":"367-379","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological targeting of the integrated stress response by 2BAct improves object recognition memory and reduces neuroinflammation in the 5xFAD model of Alzheimer's disease"],"prefix":"10.1177","volume":"112","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0109-8962","authenticated-orcid":false,"given":"Daegeon","family":"Kim","sequence":"first","affiliation":[{"name":"Yeungnam University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hojung","family":"Jeong","sequence":"additional","affiliation":[{"name":"Yeungnam University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Kyung","family":"Lim","sequence":"additional","affiliation":[{"name":"Yeungnam University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Min","family":"Ahn","sequence":"additional","affiliation":[{"name":"Gangnam Severance Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minseok","family":"Song","sequence":"additional","affiliation":[{"name":"Yeungnam University"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2026,5,25]]},"reference":[{"key":"e_1_3_3_2_2","volume-title":"World Alzheimer Report 2019: Attitudes to dementia. 2019","author":"Alzheimer\u2019s Disease International","year":"2019","unstructured":"Alzheimer\u2019s Disease International. 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