MicroRNA ‐3473b regulates the expression of TREM2/ULK1 and inhibits autophagy in inflammatory pathogenesis of Parkinson’s disease

AbstractParkinson's disease （PD） is a neurodegenerative disease characterized by selective loss of dopaminergic（DA） neurons in the midbrain. The regulatory role of a variety of microRNAs in Parkinson's disease has been confirmed, and our study is the first to demonstrate that miR‐3473b is involved in the regulation o f Parkinson's disease. In vitro, an miR‐3473b inhibitor can inhibit the secretion of inflammatory factors (TNF‐α and IL‐1β) in moues microglia cell line(BV2) cells induced by lipopolysaccharide(LPS) and promote autophagy in BV2 cells. In vivo, miR‐3473b antagomir can inhibit the activation of substantia nigra pars compacta (SNpc) microglia of C57BL/6 mice induced by 1‐Methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine(MPTP) and promote autophagy. Deletion of TREM2, one of the most highly expressed receptors in microglia, leads to the occurrence and development of PD. ULK1 is a comp onent of the Atg1 complex. Deletion of ULK1 aggravates the pathological reaction of PD. TREM2 and ULK1 are predicted potential targets of miR‐3473b by Targetscan. Then, the results of our experiments indicate that transfection with a miR‐3473b mimic can inhibit the expression of TREM2 and ULK1. Data from a double luciferase experiment indicate that the 3'‐UTR of TREM2, but not ULK1, is the direct target of miR‐3473b. Then we aim to investigate the regulation of TREM2 and ULK1 in PD. We found that the expression of p‐ULK1 was significantly increased via u...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research