Bone marrow mesenchymal stem cell-derived exosome (BMSCs-Exo)-derived TNF-stimulated gene-6 (TSG-6) has anti-inflammatory and antioxidative stress-related properties that may be beneficial in the treatment of Parkinson disease (PD) patients. To elucidate the mechanisms involved, we analyzed the effects of BMSCs-Exo-derived TSG-6 on in vitro models of PD induced with 1-methyl-4-phenylpyridinium (MPP+). TSG-6 was abundant in BMSCs-Exo and it attenuated MPP+-induced neurotoxicity. Moreover, BMSCs-Exo reversed the MPP+-induced toxicity accelerated by neural precursor cells expressed developmentally downregulated 4 (NEDD4) knockdown or miR-7 mimics. Further analysis indicated that NEDD4 combined with leucine-rich repeat kinase 2 (LRRK2) to accelerate ubiquitin degradation of LRRK2. Signal transducer and activator of transcription 3 (STAT3) bound to the miR-7 promoter and miR-7 targeted NEDD4. These data indicate that BMSCs-Exo-derived TSG-6 attenuated neurotoxicity via the STAT3-miR-7-NEDD4 axis. Our results define the specific mechanisms for BMSCs-Exo-derived TSG-6 regulation of MPP+-induced neurotoxicity that are relevant to understanding PD pathogenesis and developing therapies for PD patients.
Keywords: BMSCs-Exo; Neurotoxicity; Parkinson disease; TSG-6.
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