PEP-1-SOD fusion protein efficiently protects against paraquat-induced dopaminergic neuron damage in a Parkinson disease mouse model.
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.
Choi
Hee Soon
HS
Department of Biomedical Science and Research Institute for Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Korea.
An
Jae Jin
JJ
Kim
So Young
SY
Lee
Sun Hwa
SH
Kim
Dae Won
DW
Yoo
Ki-Yeon
KY
Won
Moo Ho
MH
Kang
Tae-Cheon
TC
Kwon
Hyung Joo
HJ
Kang
Jung Hoon
JH
Cho
Sung-Woo
SW
Kwon
Oh-Shin
OS
Park
Jinseu
J
Eum
Won Sik
WS
Choi
Soo Young
SY
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
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