title: The potential neuroprotection mechanism of GDNF in the 6-OHDA-induced cellular models of Parkinson's Disease.
abstract: The glial cell line-derived neurotrophic factor (GDNF) potential as a therapeutic agent for the treatment of Parkinson's Disease (PD) has been extensively explored. However, the mechanism of the GDNF neuroprotective effects is still unclear. In this study, the neuroprotective mechanism of the GDNF in the PD cellular models, which was obtained by the 6-hydroxydopamine (6-OHDA)-induced dopaminergic (DA) cell line MN9D damage was investigated by microarray. Interestingly, 54 constitutively increased or decreased genes were detected, 17 of which have not been reported previously. The expression of 5 up-regulated and 5 down-regulated genes which displayed the most obvious changes compared to the no GDNF treatment cells and was previously proven to be related to cell survival was validated by real-time PCR and western blot. Moreover, the up-regulated gene Ager and down-regulated gene Ccnl2 which were related to the PI-3K/Akt signaling pathway, but not researched in the neuron-cells, were investigated by overexpression and RNA interference. Overexpression of Ager or knockdown the expression of Ccnl2 decreased the damage to MN9D cells caused by 6-OHDA and reduced their apoptosis. All these results suggested that the protective effects of the GDNF on the 6-OHDA damaged MN9D cells could be understood by enhancing the expression of the apoptosis inhibiting genes and decreasing the expression of the apoptosis promoting genes. Thus, this study might provide a number of specific candidates and potential targets to investigate the protective mechanism of GDNF in DA neurons.
authors.affiliation: Department of Neurobiology and Anatomy, Xuzhou Medical College, Huaihai West Street 84, Xuzhou, Jiangsu, People's Republic of China.
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Meng
authors.initials: M
authors.lastname: Wang
authors.forename: Shuan
authors.initials: S
authors.lastname: Zhu
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Ye
authors.initials: Y
authors.lastname: Xiong
authors.forename: Dian-Shuai
authors.initials: DS
authors.lastname: Gao
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D016000:Cluster Analysis; D016213:Cyclins / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D055785:Gene Knockdown Techniques; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology / Q000627:therapeutic use*; D051379:Mice; D008954:Models, Biological; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D020411:Oligonucleotide Array Sequence Analysis; D016627:Oxidopamine; D010300:Parkinson Disease / Q000188:drug therapy*; D060888:Real-Time Polymerase Chain Reaction; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000378:metabolism; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics
chemical_list: C499078:Ccnl2 protein, mouse; D016213:Cyclins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D016627:Oxidopamine