Journal
MOLECULAR THERAPY-NUCLEIC ACIDS
Volume 23, Issue -, Pages 1334-1344Publisher
CELL PRESS
DOI: 10.1016/j.omtn.2021.01.022
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- Peking Union Medical College Hospital
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Parkinson's disease is the second most common neuro-degenerative disease characterized by irreversible damage of dopamine neurons. Studies have shown that NLRP3 inflammasome and CDK5-mediated autophagy are important in PD. miR-188-3p is a potential therapeutic target for treating PD.
Parkinson's disease (PD) is the second-most common neuro-degenerative disease after Alzheimer's disease. The most important pathological feature of PD is the irreversible damage of dopamine neurons, which is related to autophagy and neuroinflammation in the substantia nigra. Previous studies found that the activation of NAcht Leucine-rich repeat Protein 3 (NLRP3) inflammasome/pyroptosis and cell division protein kinase 5 (CDK5)-mediated autophagy played an important role in PD. Bioinformatics analyses further predicted that microRNA (miR)-188-3p potentially targets NLRP3 and CDK5. Adipose-derived stem cell (ADSC)-derived exosomes were found to be excellent vectors for genetic therapy. We assessed the levels of injury, autophagy, and inflammasomes in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP)-induced PD mice models and neurotoxin 1-methyl-4-phenylpyridinium (MPP+)-induced cell models after treating them with miR-188- 3p-enriched exosomes. miR-188-3p-enriched exosome treatment suppressed autophagy and pyroptosis, whereas increased proliferation via targeting CDK5 and NLRP3 in mice and MN9D cells. It was revealed that mir-188-3p could be a new therapeutic target for curing PD patients.
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