title: MiR-133b ameliorates axon degeneration induced by MPP(+) via targeting RhoA.
abstract: Increasing evidence suggests that microRNAs (miRs) play a significant role in the pathogenesis of Parkinson's disease (PD). MiR-133b, which is significantly decreased in the PD midbrain, has recently been shown to promote neurite outgrowth and enhance neural functional recovery. However, the role of miR-133b in PD has not been clearly established. Here, using a well-established PD model culture based on the neurotoxin 1-methyl-4-phenyl-pyridinium (MPP(+)), we demonstrated that miR-133b could promote axon outgrowth in dopaminergic neurons (DNs) and ameliorated MPP(+)-induced axon degeneration. Additional experiments suggested that the mechanisms of this miR-133b-mediated effect might rely on RhoA inhibition. We demonstrated that RhoA, an inhibitor of axonal growth, was increased in DNs under MPP(+) treatment, and this increase could be attenuated by miR-133b overexpression. Moreover, we demonstrated that the induced expression of miR-133b could inhibit α-synuclein, which is critically involved in the pathological process of PD. Furthermore, we found that overexpression of miR-133b abrogated the MPP(+)-induced decrease in the Bcl-2/Bax ratio and upregulated phosphorylated Akt (p-Akt), which is a pro-survival kinase. Together these findings reveal novel roles for miR-133b in the pathogenesis of PD and provide new therapeutic avenues for the treatment of the disease.
authors.affiliation: Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: M
authors.initials: M
authors.lastname: Niu
authors.affiliation: Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: R
authors.initials: R
authors.lastname: Xu
authors.affiliation: Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: J
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China.
authors.forename: B
authors.initials: B
authors.lastname: Hou
authors.affiliation: Department of Neurology, The Affiliated Hospital of Qingdao University, Qingdao, China. Electronic address: xieanmu@163.com.
authors.forename: A
authors.initials: A
authors.lastname: Xie
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001369:Axons / Q000187:drug effects / Q000473:pathology*; D002478:Cells, Cultured; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D016501:Neurites / Q000187:drug effects / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism*; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D020742:rhoA GTP-Binding Protein / Q000378:metabolism*
chemical_list: C549446:MIRN133 microRNA, rat; D035683:MicroRNAs; D051057:Proto-Oncogene Proteins c-akt; D020742:rhoA GTP-Binding Protein; D015655:1-Methyl-4-phenylpyridinium
keywords: MiR-133b; Parkinson’s disease; RhoA; alpha-synuclein; axon degeneration