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
Hauptverfasser: Retinasamy, Thaarvena, Lee, Amber Lot Yee, Lee, Hsien Siang, Lee, Vanessa Lin Lin, Shaikh, Mohd Farooq, Yeong, Keng Yoon
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Sprache:eng
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Zusammenfassung: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.
ISSN:1948-7193
1948-7193
DOI:10.1021/acschemneuro.4c00205