miR‐30b protects nigrostriatal dopaminergic neurons from MPP(+)‐induced neurotoxicity via SNCA

Abstract

Objective To explore the function of miR‐30b in pathogenesis of Parkinson's disease (PD) and its underlying molecular mechanism. Materials and Methods We used 1‐methyl‐4‐phenyl‐1,2,3,6‐tetrahydropyridine (MPP(+)) as a tool for constructing the PD cell model, using miR‐30b mimics or inhibitors to manipulate miR‐30b level for an experimental model of acquisition. The cell viability of SH‐SY5Y was detected by CCK, and luciferase was used to screen the binding of target genes. The protein levels of SNCA were measured by Western blot. Then, we investigate the changes in pro‐ and anti‐apoptotic markers with or without miR‐30b treatment. Results There was a significant low expression of MiR‐30b in MPP(+)‐induced cells. SH‐SY5Y cell viability was rescued by MiR‐30b overexpression. Luciferase experiments showed that MiR‐30b may bind to the 3′‐UTR side of SNCA and inhibited its expression. By Western blot, the SNCA level was markedly decreased by miR‐30b. miR‐30b attenuated the upregulation of Bax and the depletion of Bcl‐2 induced by MPP(+).

miR‐30b Promotes spinal cord sensory function recovery via the Sema3A/NRP‐1/PlexinA1/RhoA/ROCK Pathway

“…15,16,42 MiR-30b could protect cell from MPP(+) treatment. 19 Neuropathic pain could be relieved by miR-30b overexpression. [20][21][22] In this study, we wanted to clarify one of the mechanisms underlying axon growth regulation.…”

“…Previous studies have proven that miRNAs can regulate neuronal axon growth via different pathways 15,16,42 . MiR‐30b could protect cell from MPP(+) treatment 19 . Neuropathic pain could be relieved by miR‐30b overexpression 20‐22 .…”

“…Meanwhile, they are widely expressed in both the central nerve system and peripheral nerve system and have been shown to be involved in regulation of neuronal axon growth ability 17,18 . In Parkinson's disease, miR‐30b shows cytoprotective role via targeting SNCA and inhibiting cell apoptosis 19 . MiR‐30b overexpression relieves neuropathic pain 20‐22 .…”

Dietary Antioxidants and Parkinson’s Disease

“…Antiapoptotic proteins Bcl-2 and Bcl-xL are reported to block apoptosis by directly binding proapoptotic Bcl-2 proteins. Upregulation of proapoptotic proteins such as Bax and Bim as well as of other mechanisms including caspase activation and cytoplasmic release of cytochrome c have been reported in various PD models [ 54 , 56 , 57 , 58 , 59 , 60 ]. Transgenic mice lacking Bax are resistant to MPTP-induced neuronal death in the SNpc [ 56 ], and application of microRNA (miR) including miR216a and miR7 targeting Bax are protective against MPTP treatment in an in vitro and in vivo PD models [ 61 , 62 ].…”

Anti-Apoptotic Effects of Carotenoids in Neurodegeneration

“…Loss of dopaminergic neurons in the substantia nigra results in Parkinson's disease. Although autophagy and necrosis are also involved during neurodegeneration, apoptotic features including increased abundance of pro-apoptotic Bcl-2 protein, activation of caspases, and cytochrome c release are found during progression of Parkinson's disease [39][40][41]. Mitochondrial dysfunction, particularly impairment of complex I, is a key feature of Parkinson's pathology [42][43][44].…”