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  • Title: MicroRNA-185 activates PI3K/AKT signalling pathway to alleviate dopaminergic neuron damage via targeting IGF1 in Parkinson's disease.
    Author: Qin X, Zhang X, Li P, Wang M, Yan L, Pan P, Zhang H, Hong X, Liu M, Bao Z.
    Journal: J Drug Target; 2021 Sep; 29(8):875-883. PubMed ID: 33560148.
    Abstract:
    OBJECTIVES: Studies have extensively explored the role of microRNAs (miRs) in Parkinson's disease (PD) and miR-185 is related to autophagy and apoptosis of dopaminergic neurons in PD. However, the role of miR-185 mediating insulin-like growth factor 1 (IGF1)/phosphatidylinositol-3-kinase/protein kinase B signalling pathway (PI3K/AKT) in PD still needs in-depth exploration. METHODS: Rat PD models were established by injection of 6-hydroxydopamine. PD rats were injected with miR-185 or insulin-like growth factor 1 (IGF1)-related sequences. Behaviour tests were performed, oxidative stress-related factors, tyrosine hydroxylase (TH)-, glial fibrillary acidic protein (GFAP)-, ionised calcium-binding adaptor molecule-1 (Iba-1)- and TUNEL-positive cells in the substantia nigra were determined. Levels of miR-185, IGF1 and phosphatidylinositol-3-kinase/protein kinase B (PI3K/AKT) signalling pathway-related factors were also detected. RESULTS: miR-185 level was reduced in rats with PD. Restoring miR-185 promoted behaviour functions, ameliorated pathological damages and oxidative stress, increased TH-positive dopaminergic neurons, decreased GFAP- and Iba-1-positive cells and restrained neuronal apoptosis in the substantia nigra in PD rats. miR-185 targeted IGF1 to activate PI3K/AKT signalling pathway. Up-regulation of IGF1 mitigated restored miR-185-mediated effects on PD rats. CONCLUSION: This study illustrates that miR-185 ameliorates dopaminergic neuron damage via targeting IGF1 and activating PI3K/AKT signalling pathway in PD, which renews the therapy for PD.
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