Repurposing Anakinra for Alzheimer’s Disease: The In Vitro and In Vivo Effects of Anakinra on LPS- and AC-Induced Neuroinflammation
Alzheimer’s disease is a significant global health issue, and studies suggest that neuroinflammation plays a vital role in the advancement of this disease. In this study, anakinra has been shown to display a time- and concentration-dependent antineuroinflammatory effect. In the in vitro studies, it...
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| Veröffentlicht in: | ACS chemical neuroscience 2024-09, Vol.15 (18), p.3298-3310 |
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| creator | Retinasamy, Thaarvena Lee, Amber Lot Yee Lee, Hsien Siang Lee, Vanessa Lin Lin Shaikh, Mohd Farooq Yeong, Keng Yoon |
| description | Alzheimer’s disease is a significant global health issue, and studies suggest that neuroinflammation plays a vital role in the advancement of this disease. In this study, anakinra has been shown to display a time- and concentration-dependent antineuroinflammatory effect. In the in vitro studies, it diminished the gene expressions of tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO) synthase 2 stimulated by lipopolysaccharide (LPS). Anakinra also reduced the LPS-induced production of NO and reactive oxygen species. Thus, the hypertrophic state of LPS-activated BV2 microglial cells was reversed by anakinra. Furthermore, acrylamide (ACR)-induced activation of nuclear transcription factor-κB, TNF-α, and interleukin-1β was downregulated, while cAMP response element binding protein and brain-derived neurotrophic factor expression levels were markedly enhanced in ACR-treated zebrafish larvae. It was also observed that anakinra improved the uncoordinated swimming behaviors in ACR-exposed zebrafish larvae. Overall, anakinra demonstrated potential antineuroinflammatory and antioxidative effects. |
| doi_str_mv | 10.1021/acschemneuro.4c00205 |
| format | Article |
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Neurosci</addtitle><description>Alzheimer’s disease is a significant global health issue, and studies suggest that neuroinflammation plays a vital role in the advancement of this disease. In this study, anakinra has been shown to display a time- and concentration-dependent antineuroinflammatory effect. In the in vitro studies, it diminished the gene expressions of tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO) synthase 2 stimulated by lipopolysaccharide (LPS). Anakinra also reduced the LPS-induced production of NO and reactive oxygen species. Thus, the hypertrophic state of LPS-activated BV2 microglial cells was reversed by anakinra. Furthermore, acrylamide (ACR)-induced activation of nuclear transcription factor-κB, TNF-α, and interleukin-1β was downregulated, while cAMP response element binding protein and brain-derived neurotrophic factor expression levels were markedly enhanced in ACR-treated zebrafish larvae. It was also observed that anakinra improved the uncoordinated swimming behaviors in ACR-exposed zebrafish larvae. Overall, anakinra demonstrated potential antineuroinflammatory and antioxidative effects.</description><subject>Alzheimer Disease - drug therapy</subject><subject>Alzheimer Disease - metabolism</subject><subject>Animals</subject><subject>Anti-Inflammatory Agents - pharmacology</subject><subject>Drug Repositioning - methods</subject><subject>Interleukin 1 Receptor Antagonist Protein - pharmacology</subject><subject>Interleukin-1beta - metabolism</subject><subject>Lipopolysaccharides - pharmacology</subject><subject>Mice</subject><subject>Microglia - drug effects</subject><subject>Microglia - metabolism</subject><subject>Neuroinflammatory Diseases - drug therapy</subject><subject>Nitric Oxide - metabolism</subject><subject>Nitric Oxide Synthase Type II - metabolism</subject><subject>Reactive Oxygen Species - metabolism</subject><subject>Tumor Necrosis Factor-alpha - metabolism</subject><subject>Zebrafish</subject><issn>1948-7193</issn><issn>1948-7193</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kctO3DAUhi1Exf0NUOUlm1Bfcu0umg7tSKO2AtptdHCOGU8TO9hJJbpi04fg9XiShmZoZ8XKx9b3_8fn_ISccnbOmeDvQAW1wtbi4N15rBgTLNkhB7yI8yjjhdzdqvfJYQhrxtKC5eke2ZeF4DIR_ID8vsRu8J0Lxt7S0sIPYz1Q7Twtm18rNC36p4fHQD-YgBDwPb1eIV1Y-t303lGw9XT56ehca1R9oE7_93GWLr9eRX-5chYtbD0orOnn5z8bqxtoW-iNs8fkjYYm4MnmPCLfLubXs0_R8svHxaxcRiBE1keZuklqXaegWF3wFOT4rJNxKCEhhUImDDMhxw6Q6CxTkMW8zjTLYxQ8xxzkETmbfDvv7gYMfdWaoLBpwKIbQiVZUeQsTng8ovGEKu9C8KirzpsW_H3FWfUcQLUdQLUJYJS93XQYblqs_4leNj4CbAJGebV2g7fjwK97_gH0vJcP</recordid><startdate>20240918</startdate><enddate>20240918</enddate><creator>Retinasamy, Thaarvena</creator><creator>Lee, Amber Lot Yee</creator><creator>Lee, Hsien Siang</creator><creator>Lee, Vanessa Lin Lin</creator><creator>Shaikh, Mohd Farooq</creator><creator>Yeong, Keng Yoon</creator><general>American Chemical Society</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><orcidid>https://orcid.org/0009-0006-0755-7620</orcidid><orcidid>https://orcid.org/0000-0003-0433-5070</orcidid></search><sort><creationdate>20240918</creationdate><title>Repurposing Anakinra for Alzheimer’s Disease: The In Vitro and In Vivo Effects of Anakinra on LPS- and AC-Induced Neuroinflammation</title><author>Retinasamy, Thaarvena ; Lee, Amber Lot Yee ; Lee, Hsien Siang ; Lee, Vanessa Lin Lin ; Shaikh, Mohd Farooq ; Yeong, Keng Yoon</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a227t-7cb5dfd6ac0d916a3a22f569023a6a9350e723ceda5f77ca741d7f084e218e8a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Alzheimer Disease - drug therapy</topic><topic>Alzheimer Disease - metabolism</topic><topic>Animals</topic><topic>Anti-Inflammatory Agents - pharmacology</topic><topic>Drug Repositioning - methods</topic><topic>Interleukin 1 Receptor Antagonist Protein - pharmacology</topic><topic>Interleukin-1beta - metabolism</topic><topic>Lipopolysaccharides - pharmacology</topic><topic>Mice</topic><topic>Microglia - drug effects</topic><topic>Microglia - metabolism</topic><topic>Neuroinflammatory Diseases - drug therapy</topic><topic>Nitric Oxide - metabolism</topic><topic>Nitric Oxide Synthase Type II - metabolism</topic><topic>Reactive Oxygen Species - metabolism</topic><topic>Tumor Necrosis Factor-alpha - metabolism</topic><topic>Zebrafish</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Retinasamy, Thaarvena</creatorcontrib><creatorcontrib>Lee, Amber Lot Yee</creatorcontrib><creatorcontrib>Lee, Hsien Siang</creatorcontrib><creatorcontrib>Lee, Vanessa Lin Lin</creatorcontrib><creatorcontrib>Shaikh, Mohd Farooq</creatorcontrib><creatorcontrib>Yeong, Keng Yoon</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>ACS chemical neuroscience</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Retinasamy, Thaarvena</au><au>Lee, Amber Lot Yee</au><au>Lee, Hsien Siang</au><au>Lee, Vanessa Lin Lin</au><au>Shaikh, Mohd Farooq</au><au>Yeong, Keng Yoon</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Repurposing Anakinra for Alzheimer’s Disease: The In Vitro and In Vivo Effects of Anakinra on LPS- and AC-Induced Neuroinflammation</atitle><jtitle>ACS chemical neuroscience</jtitle><addtitle>ACS Chem. Neurosci</addtitle><date>2024-09-18</date><risdate>2024</risdate><volume>15</volume><issue>18</issue><spage>3298</spage><epage>3310</epage><pages>3298-3310</pages><issn>1948-7193</issn><eissn>1948-7193</eissn><abstract>Alzheimer’s disease is a significant global health issue, and studies suggest that neuroinflammation plays a vital role in the advancement of this disease. In this study, anakinra has been shown to display a time- and concentration-dependent antineuroinflammatory effect. In the in vitro studies, it diminished the gene expressions of tumor necrosis factor-alpha (TNF-α) and nitric oxide (NO) synthase 2 stimulated by lipopolysaccharide (LPS). Anakinra also reduced the LPS-induced production of NO and reactive oxygen species. Thus, the hypertrophic state of LPS-activated BV2 microglial cells was reversed by anakinra. 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| subjects | Alzheimer Disease - drug therapy Alzheimer Disease - metabolism Animals Anti-Inflammatory Agents - pharmacology Drug Repositioning - methods Interleukin 1 Receptor Antagonist Protein - pharmacology Interleukin-1beta - metabolism Lipopolysaccharides - pharmacology Mice Microglia - drug effects Microglia - metabolism Neuroinflammatory Diseases - drug therapy Nitric Oxide - metabolism Nitric Oxide Synthase Type II - metabolism Reactive Oxygen Species - metabolism Tumor Necrosis Factor-alpha - metabolism Zebrafish |
| title | Repurposing Anakinra for Alzheimer’s Disease: The In Vitro and In Vivo Effects of Anakinra on LPS- and AC-Induced Neuroinflammation |
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