1-Deoxynojirimycin attenuates pathological markers of Alzheimer's disease in the in vitro model of neuronal insulin resistance.
Autor: | Parida IS; Laboratory of Food Function Analysis, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.; Schizophrenia Research Project, Department of Psychiatry and Behavioral Sciences, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan., Takasu S; Laboratory of Food Function Analysis, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan.; Laboratory of Pharmaceutical Analytical Chemistry, Gifu Pharmaceutical University, Gifu, Japan., Ito J; Laboratory of Food Function Analysis, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan., Eitsuka T; Laboratory of Food Function Analysis, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan., Nakagawa K; Laboratory of Food Function Analysis, Graduate School of Agricultural Science, Tohoku University, Sendai, Japan. |
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Jazyk: | angličtina |
Zdroj: | FASEB journal : official publication of the Federation of American Societies for Experimental Biology [FASEB J] 2024 Jul 15; Vol. 38 (13), pp. e23800. |
DOI: | 10.1096/fj.202302600R |
Abstrakt: | Insulin resistance, the hallmark of type 2 diabetes mellitus (T2DM), has emerged as a pathological feature in Alzheimer's disease (AD). Given the shared role of insulin resistance in T2DM and AD, repurposing peripheral insulin sensitizers is a promising strategy to preserve neuronal insulin sensitivity and prevent AD. 1-Deoxynojirimycin (DNJ), a bioactive iminosugar, exhibited insulin-sensitizing effects in metabolic tissues and was detected in brain tissue post-oral intake. However, its impact on brain and neuronal insulin signaling has not been described. Here, we investigated the effect of DNJ treatment on insulin signaling and AD markers in insulin-resistant human SK-N-SH neuroblastoma, a cellular model of neuronal insulin resistance. Our findings show that DNJ increased the expression of insulin signaling genes and the phosphorylation status of key molecules implicated in insulin resistance (Y1146-pIRβ, S473-pAKT, S9-GSK3B) while also elevating the expression of glucose transporters Glut3 and Glut4, resulting in higher glucose uptake upon insulin stimuli. DNJ appeared to mitigate the insulin resistance-driven increase in phosphorylated tau and Aβ (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.) |
Databáze: | MEDLINE |
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