Reactive astrocytes targeting with oral vitamin A: Efficient neuronal regeneration for Parkinson's disease treatment and reversal of associated liver fibrosis

口服维生素 A 靶向反应性星形胶质细胞:有效的神经元再生,用于治疗帕金森病和逆转相关的肝纤维化

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作者:Nesrine Saeid El-Mezayen, Mennat-Allah Magdy Attia, Mohanad Yehia Shafik, Hadeer Galal Gowied, Hadeer Ahmed Abdel-Aal, Sara Medhat Abdel-Hady, Mostafa Said Ghazy

Conclusion

VA -medium dose pursued brain targeting in PD with the potential capability of regenerating neurons and restoring dopaminergic transmission. This may place this therapy as an essential treatment in PD management protocol.

Methods

Fluorescently labeled VA -coupled liposomes (FLV) were traced using confocal laser microscope in rats with induced PD for detecting brain accumulation and uptake into fluorescently labeled astrocytes. Liver fibrosis associated with PD was assessed biochemically and histopathologically, while VA deficiency was confirmed by assessing retinol-binding protein gene expression in the brain and liver. Multiple VA doses were tested for reversing PD-associated liver fibrosis, generating TFs (involved in reprograming astrocytes/fibroblasts into different neuronal types) and capability of dopaminergic-neurons regeneration.

Results

Fluorescently labeled VA -coupled liposomes revealed selective brain accumulation and uptake into astrocytes. PD was associated with significant liver fibrosis and VA deficiency in the brain and liver. Furthermore, VA -medium dose (VAMD) was the optimum one for reversing PD-associated liver fibrosis, generating multiple astrocytes/fibroblasts reprogramming TFs, regenerating dopaminergic neurons, and improving PD.

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