title: Deficiency of Trim27 protects dopaminergic neurons from apoptosis in the neurotoxin model of Parkinson's disease.
abstract: Parkinson's disease (PD) is an age-related neurodegenerative movement disorder, characterized by loss of dopaminergic neurons in the substantia nigra pars compacta (SNpc). The MPTP/MPP+ model is often used to investigate the signaling mechanisms of dopamine (DA) degeneration, both in vivo and in vitro. The identification of specific genetic and environmental factors responsible for PD has bolstered evidence for a shared pathway of neuronal death -apoptosis. Trim27 is reported to promote apoptosis. However, little evidence exists to indicate a linkage between Trim27 and PD. In this study, we found that compared to healthy individuals, Trim27 was significantly upregulated in patients with PD. We further showed that Trim27 expression was dramatically induced in PC12 cells and in the SNpc of the PD mouse model. RNAi-mediated knockdown of Trim27 in PC12 cells showed obvious suppression of apoptosis. There are reduced dopaminergic neuron loss and lower apoptotic protein expression levels in MPTP-treated Trim27-/- mice, compared with MPTP-treated WT mice. These data demonstrated that Trim27 deficiency decreases apoptosis and protects dopaminergic neurons in the neurotoxin model of PD, suggesting that Trim27 may be an effective potential target during the treatment of PD.
authors.affiliation: Department of Neurology, First Hospital, Jilin University, Jilin, 130021, China; Department of Neurology, The Hospital of Heilongjiang Province, Harbin, 150000, China.
authors.forename: YongDan
authors.initials: Y
authors.lastname: Liu
authors.affiliation: School of Electrical Engineering and Automation, Harbin Institute of Technology, Harbin, 150000, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhu
authors.affiliation: Department of Neurology, Hebei Medical University, Shijiazhuang, 050017, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Department of Neurology, First Hospital, Jilin University, Jilin, 130021, China.
authors.forename: XueLi
authors.initials: X
authors.lastname: Fan
authors.affiliation: Department of Neurology, The Hospital of Heilongjiang Province, Harbin, 150000, China.
authors.forename: ZhongYuan
authors.initials: Z
authors.lastname: Piao
authors.affiliation: Department of Neurology, First Hospital, Jilin University, Jilin, 130021, China. Electronic address: xmjiang_bio@163.com.
authors.forename: XinMei
authors.initials: X
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D059290:Dopaminergic Neurons / Q000502:physiology*; D055785:Gene Knockdown Techniques; D006801:Humans; D020267:MPTP Poisoning / Q000503:physiopathology*; D008297:Male; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D010300:Parkinson Disease / Q000503:physiopathology*; D065842:Pars Compacta / Q000503:physiopathology; D051381:Rats; D044767:Ubiquitin-Protein Ligases; D000070584:Tripartite Motif Proteins
chemical_list: D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D044767:Ubiquitin-Protein Ligases; C064419:TRIM27 protein, human; D000070584:Tripartite Motif Proteins; C489295:Trim27 protein, rat; C489296:Trim27 protein, mouse
keywords: Apoptosis; MPTP; Parkinson׳s Disease; Trim27