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Current Development of siRNA Bioconjugates: From Research to the Clinic
In this study, it was shown that the main factor determining the nature of the biodistribution of conjugates is their lipophilicity. Conjugates of siRNA with lower lipophilicity; i.e., derivatives of retinoic acid, lithocholic acid, and docosahexanoic acid with greater efficiency than cholesterol conjugates accumulated in the kidneys, bladder, and lungs of the mouse after subcutaneous injection (Biscans et al., 2018). This fact is consistent with previous data that showed that more lipophilic conjugates bind more efficiently to serum components, and thus are not excreted by the kidneys (Wolfrum et al., 2007; Osborn et al.,...
Source: Frontiers in Pharmacology - April 25, 2019 Category: Drugs & Pharmacology Source Type: research

SIRT2 regulates insulin sensitivity in insulin-resistant neuronal cells.
In this study, we report the role of SIRT2 in regulating insulin-sensitivity in neuronal cells in vitro. Using approaches like pharmacological inhibition of SIRT2, siRNA mediated SIRT2 knockdown and over-expression of wild-type and catalytically-mutated SIRT2, we observed that downregulation of SIRT2 ameliorated the reduced activity of AKT and increased insulin-stimulated glucose uptake in insulin resistant neuro-2a cells. The data was supported by over expression of catalytically-inactive SIRT2 in insulin-resistant human SH-SY5Y neuronal cells. Data highlights a crucial role of SIRT2 in regulation of neuronal insulin sens...
Source: Biochemical and Biophysical Research communications - May 5, 2016 Category: Biochemistry Authors: Arora A, Dey CS Tags: Biochem Biophys Res Commun Source Type: research