title: PEP-1-SOD fusion protein efficiently protects against paraquat-induced dopaminergic neuron damage in a Parkinson disease mouse model.
abstract: Parkinson disease (PD) is a common neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra (SN). However, the mechanism of the pathology of PD still remains poorly understood. Because the administration of the herbicide paraquat triggers selective dopaminergic neuronal cell death, exposure of mice to this herbicide is one valuable model for studying the pathological aspects of PD. In this study, we investigated the protective effects of PEP-1-SOD in vitro and in vivo under exposure to the herbicide paraquat. The viability of neuronal cells treated with paraquat was markedly increased by transduced PEP-1-SOD. When the PEP-1-SOD fusion protein was injected intraperitoneally into mice, a completely protective effect against dopaminergic neuronal cell death in the SN was observed. This protective effect was synergistically increased when the PEP-1-SOD was cotransduced with Tat-alpha-synuclein. These results suggest that PEP-1-SOD provides a strategy for therapeutic delivery in various human diseases related to reactive oxygen species, including PD.
authors.affiliation: Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
authors.forename: Hee Soon
authors.initials: HS
authors.lastname: Choi
authors.forename: Jae Jin
authors.initials: JJ
authors.lastname: An
authors.forename: So Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Sun Hwa
authors.initials: SH
authors.lastname: Lee
authors.forename: Dae Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Ki-Yeon
authors.initials: KY
authors.lastname: Yoo
authors.forename: Moo Ho
authors.initials: MH
authors.lastname: Won
authors.forename: Tae-Cheon
authors.initials: TC
authors.lastname: Kang
authors.forename: Hyung Joo
authors.initials: HJ
authors.lastname: Kwon
authors.forename: Jung Hoon
authors.initials: JH
authors.lastname: Kang
authors.forename: Sung-Woo
authors.initials: SW
authors.lastname: Cho
authors.forename: Oh-Shin
authors.initials: OS
authors.lastname: Kwon
authors.forename: Jinseu
authors.initials: J
authors.lastname: Park
authors.forename: Won Sik
authors.initials: WS
authors.lastname: Eum
authors.forename: Soo Young
authors.initials: SY
authors.lastname: Choi
mesh_terms: D000818:Animals; D001253:Astrocytes; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D004795:Enzyme Stability; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology*; D010300:Parkinson Disease / Q000473:pathology* / Q000517:prevention & control*; D011993:Recombinant Fusion Proteins; D012697:Serine Endopeptidases / Q000008:administration & dosage / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000008:administration & dosage / Q000494:pharmacology*; D051844:alpha-Synuclein / Q000378:metabolism
chemical_list: D015259:Dopamine Agents; D018840:HSP70 Heat-Shock Proteins; D011993:Recombinant Fusion Proteins; D051844:alpha-Synuclein; D013482:Superoxide Dismutase; C097082:Pep1 protein, mouse; D012697:Serine Endopeptidases; D010269:Paraquat