Project description:The effect of three individual SCFA were tested in primary microglial cultured cells, we evaluate microglia transcriptome using Nanostring technology
Project description:Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons, with neuroinflammation playing a critical role in disease progression. The transcription factor SIX2 has been identified as an anti-inflammatory factor in microglial cells; however, the underlying mechanisms remain poorly understood. In this study, we demonstrated that SIX2 overexpression protects dopaminergic cells by promoting the polarization of microglial cells from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Mechanistically, SIX2 upregulates DDIT4 expression by binding to its promoter region. DDIT4, in turn, facilitates microglial M2 polarization by inhibiting mTOR, thereby activating autophagy. Furthermore, SIX2-induced M2-polarized microglial cells secrete exosomes carrying miR-3470b. These exosomes are taken up by dopaminergic neurons, where miR-3470b inhibits GREM1 expression and enhances TGF-β signaling activity. Consequently, SIX2-mediated mechanisms prevent and restore damaged dopaminergic neurons in PD mice. Our findings reveal a novel regulatory mechanism of microglial M2 polarization and provide new insights into PD immunotherapy. Additionally, the discovery of exosome-mediated miR-3470b communication between microglia and dopaminergic neurons offers a theoretical foundation for developing exosome-based miRNA therapies.
Project description:The purpose of this study was to characterize the gene expression profile of MDA-MB-231 breast cancer cells treated with various SCFA-hexosamine analogs to better understand the role of various modifications to this scaffold. Keywords: SCFA-hexosamine analog comparison
Project description:Parkinson's disease (PD) is characterized by the progressive loss of dopaminergic neurons, with neuroinflammation playing a critical role in disease progression. The transcription factor SIX2 has been identified as an anti-inflammatory factor in microglial cells; however, the underlying mechanisms remain poorly understood. In this study, we demonstrated that SIX2 overexpression protects dopaminergic cells by promoting the polarization of microglial cells from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype. Mechanistically, SIX2 upregulates DDIT4 expression by binding to its promoter region. DDIT4, in turn, facilitates microglial M2 polarization by inhibiting mTOR, thereby activating autophagy. Furthermore, SIX2-induced M2-polarized microglial cells secrete exosomes carrying miR-3470b. These exosomes are taken up by dopaminergic neurons, where miR-3470b inhibits GREM1 expression and enhances TGF-β signaling activity. Consequently, SIX2-mediated mechanisms prevent and restore damaged dopaminergic neurons in PD mice. Our findings reveal a novel regulatory mechanism of microglial M2 polarization and provide new insights into PD immunotherapy. Additionally, the discovery of exosome-mediated miR-3470b communication between microglia and dopaminergic neurons offers a theoretical foundation for developing exosome-based miRNA therapies.