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Resveratrol (RES) is a polyphenol with diverse beneficial biological and pharmacological activities, and our previous results have demonstrated its neuroprotective effects in several metabolic diseases, including non-alcoholic fatty liver disease. The aim of the present study is to investigate the potential effect of RES against oleic acid (OA)-induced cell injuries in SH-SY5Y cells and explore the possible mechanism. Based on the dose- and time-dependent effects of OA on cell proliferation and LDH release, SH-SY5Y cells were challenged with OA and incubated with or without RES (10–5–10–9 mM) or sitagliptin (STG, 10–7 mM). Lipid accumulation, SREBP1 and PPARα protein expression, glucose consumption and IRS1, AKT, ERK phosphorylation under insulin stimulation, and ROS production were detected. The protein expression of brain-derived neurotrophic factor (BDNF), Copine 6, and key molecules in the Wnt/β-catenin signalling pathway were measured via western blot. The expression of Wnt 1 was also measured via immunofluorescence staining. The results showed that RES treatment could alleviate the neurotoxicity induced by OA, as indicated by the increased cell proliferation and the decreased concentration of LDH in the supernatant. The increased lipid deposition and protein expression of SREBP1 and PPARα induced by OA was also reversed by treatment with RES. Moreover, RES could upregulate glucose consumption and the protein expression of phosphorylated IRS1, AKT, ERK and reduced ROS production in OA-induced SH-SY5Y cells. Furthermore, RES treatment reversed the imbalanced protein expression of BDNF, Copine 6, p-β-catenin, and Wnt 1 in SH-SY5Y cells induced by OA and decreased the hyperexpression of p-GSK3β. However, these effects were suppressed by DKK1, which is a specific antagonist of the Wnt signalling pathway. These results suggested that RES has a neuroprotective effect against OA-induced cell injury and dysfunctional glucolipid metabolism, and the mechanism might involve its ability to regulate oxidative stress and insulin resistance via the Wnt/β-catenin signalling pathway. [ABSTRACT FROM AUTHOR]

The FGFR3 gene encodes fibroblast growth factor receptor 3 protein, a negative regulator of chondrogenesis. Gain-of-function mutations result in constitutively activated FGFR3, leading to aberrant signal transduction, and accounting for inhibition of chondrocyte proliferation and differentiation. Generally, these pathogenic mutations maintain FGFR3 in an active state and cause diverse phenotypes in patients with skeletal dysplasia. For decades, studies have revealed the molecular mechanisms of constitutively activated FGFR3 and relevant therapeutic strategies. By modulating the FGFR3-induced signalling pathway with methods such as blocking binding between ligands and receptors, blocking tyrosine kinase activities, or antagonising the FGFR3 downstream signalling pathway, these strategies offer the possibility to ameliorate FGFR3 gene-related skeletal dysplasia phenotypes. In this review, we describe the mechanisms of potential therapeutic targets and underlying regulators and then systematically review molecular therapeutic strategies for FGFR3 gene-related skeletal dysplasia based on current knowledge. [ABSTRACT FROM AUTHOR]