Volume 25, Issue 5 (9-2021)                   ibj 2021, 25(5): 343-348 | Back to browse issues page

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Sedighi M, Baluchnejadmojarad T, Roghani M. Linagliptin Protects Human SH-SY5Y Neuroblastoma Cells against Amyloid-β Cytotoxicity via the Activation of Wnt1 and Suppression of IL-6 Release. ibj. 2021; 25 (5) :343-348
URL: http://ibj.pasteur.ac.ir/article-1-3185-en.html
Background: Alzheimer’s disease is one of the neurodegenerative disorders typified by the aggregate of amyloid-β (Aβ) and phosphorylated tau protein. Oxidative stress and neuroinflammation, because of Aβ peptides, are strongly involved in the pathophysiology of Alzheimer’s disease (AD). Linagliptin shows neuroprotective properties against AD pathological processes through alleviation of neural inflammation and AMPK activation. Methods: We assessed the benefits of linagliptin pretreatment (at 10, 20, and 50 nM concentrations), against Aβ1-42 toxicity (20 μM) in SH-SY5Y cells. The concentrations of secreted cytokines, such as TNF-α, IL-6, and IL-1β, and signaling proteins, including pCREB, Wnt1, and PKCε, were quantified by ELISA. Results: We observed that Aβ led to cellular inflammation, which was assessed by measuring inflammatory cytokines (TNF-α, IL-1β, and IL-6). Moreover, Aβ1-42 treatment impaired pCREB, PKCε, and Wnt1 signaling in human SH-SY5Y neuroblastoma cells. Addition of Linagliptin significantly reduced IL-6 levels in the lysates of cells, treated with Aβ1-42. Furthermore, linagliptin prevented the downregulation of Wnt1 in Aβ1-42-treated cells exposed. Conclusion: The current findings reveal that linagliptin alleviates Aβ1-42-induced inflammation in SH-SY5Y cells, probably through the suppression of IL-6 release, and some of its benefits are mediated through the activation of the Wnt1 signaling pathway.

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