{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T23:27:23Z","timestamp":1791502043268,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2022,5,28]],"date-time":"2022-05-28T00:00:00Z","timestamp":1653696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"Korean Government (MSIT)","doi-asserted-by":"publisher","award":["2020M3E5D9080660"],"award-info":[{"award-number":["2020M3E5D9080660"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Tyrosine-protein kinase (Syk) plays a potential role in neuroinflammation and adaptive immune responses in several neurodegenerative conditions. Seeing the significant role of Syk in the pathophysiology of neurodegeneration, several pharmacological inhibitors have been developed. One of the known inhibitors of Syk is BAY61-3606, which has shown efficacies in Alzheimer\u2019s disease (AD) through regulating amyloid production. However, little is known about its efficacies in neuroinflammation and neurodegeneration. Our finding showed that Syk expression was up-regulated by lipopolysaccharide (LPS)-dependent manner, and BAY61-3606 significantly suppressed the activated microglia (ionized calcium-binding adaptor molecule 1 [Iba-1]) and the inflammatory cytokines (tumor necrosis factor-alpha [TNF-\u03b1], interleukin 1-beta [IL-1\u03b2], IL-6) and other inflammatory mediators (nuclear factor kappa B [NF-\u03baB], cyclooxygenase-2 [Cox-2], and inducible nitric axide synthase [iNOS]) in the lipopolysaccharide (LPS)-treated in vivo and in vitro models. Moreover, BAY61-3606 significantly reduced microglia-mediated neuronal cell death by regulating the expression of Cytochrome C and Bim (B-cell lymphoma 2 [BCL-2] interacting mediator of cell death) in the LPS-treated mice brain and HT22 cells. Furthermore, the expression of synaptic markers, synaptosomal-associated protein, 25 kDa (SNAP25), synaptophysin (Syp), and postsynaptic density protein-95 (PSD95) in LPS-challenged mice showed that BAY61-3606 significantly recovered the synaptic markers. Finally, we have analyzed the effects of BAY61-3606 against memory and cognitive dysfunctions in the LPS injected mice. The Y-maze test and Passive avoidance test suggested that BAY61-3606 significantly protected against LPS-induced cognitive and memory dysfunctions. The current findings not only highlight the mechanisms of Syk in the pathophysiology of neuro-inflammation, but also support the therapeutic efficacy of BAY61-3606 in the management of neurodegeneration.<\/jats:p>","DOI":"10.3390\/cells11111777","type":"journal-article","created":{"date-parts":[[2022,5,29]],"date-time":"2022-05-29T08:50:51Z","timestamp":1653814251000},"page":"1777","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Pharmacological Inhibition of Spleen Tyrosine Kinase Suppressed Neuroinflammation and Cognitive Dysfunction in LPS-Induced Neurodegeneration Model"],"prefix":"10.3390","volume":"11","author":[{"given":"Min Woo","family":"Kim","sequence":"first","affiliation":[{"name":"Division of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9150-0155","authenticated-orcid":false,"given":"Kyonghwan","family":"Choe","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Korea"},{"name":"Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience (MHeNs), Maastricht University, 6229ER Maastricht, The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Sung","family":"Park","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyeon Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min Hwa","family":"Kang","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7411-9483","authenticated-orcid":false,"given":"Riaz","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Myeong Ok","family":"Kim","sequence":"additional","affiliation":[{"name":"Division of Life Sciences and Applied Life Science (BK 21 Four), College of Natural Science, Gyeongsang National University, Jinju 52828, Korea"},{"name":"Alz-Dementia Korea Co., Jinju 52828, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,5,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/1742-2094-1-14","article-title":"Microglia and neuroinflammation: A pathological perspective","volume":"1","author":"Streit","year":"2004","journal-title":"J. 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