Tat-Frataxin protects dopaminergic neuronal cells against MPTP-induced toxicity in a mouse model of Parkinson's disease.
Parkinson's disease (PD) is caused by various factors such as reactive oxygen species (ROS), dysfunction of mitochondria, and aggregation of misfolded proteins, thereby leading to loss of dopaminergic (DA) neurons in the substantia nigra (SN) of the brain. Frataxin (FXN) is associated with iron homeostasis and biogenesis of iron-sulfur clusters in the electron transport chain complex. In this study, we investigated the potential of Tat-FXN to cross the blood-brain barrier (BBB) and protect DA neurons against oxidative stress in a mouse model of PD. Tat-FXN was effectively transduced into SH-SY5Y cells and blocked production of ROS and cleavage of DNA, significantly improving cell survival against 1-methyl-4-phenylpyridinium induced toxicity. In addition, Tat-FXN efficiently penetrated the BBB and exhibited a clear neuroprotective effect on tyrosine hydroxylase-specific DA neurons in the SN in a mice model of 1-methyl-4-phenyl-1,2,3,6-tetra-hydropyridine-induced PD. Therefore, these results suggest that Tat-FXN may provide neuroprotective therapy for ROS related diseases including PD.
Department of Biomedical Science and Research Institute of Bioscience and Biotechnology, Hallym University, Chunchon 200-702, Republic of Korea.
Mi Jin
MJ
Kim
Dae Won
DW
Kim
Hoon Jae
HJ
Jeong
Eun Jeong
EJ
Sohn
Min Jea
MJ
Shin
Eun Hee
EH
Ahn
Soon Won
SW
Kwon
Young Nam
YN
Kim
Duk-Soo
DS
Kim
Jinseu
J
Park
Won Sik
WS
Eum
Hyun Sook
HS
Hwang
Soo Young
SY
Choi
D000447:Aldehydes / Q000378:metabolism; D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D015696:Gene Products, tat / Q000235:genetics*; D006801:Humans; D033862:Iron-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D020267:MPTP Poisoning / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009498:Neurotoxins / Q000633:toxicity*; D018384:Oxidative Stress / Q000187:drug effects; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000378:metabolism; D013997:Time Factors; D014161:Transduction, Genetic; D000096923:Frataxin
D000447:Aldehydes; D015696:Gene Products, tat; D033862:Iron-Binding Proteins; D009498:Neurotoxins; D011993:Recombinant Fusion Proteins; D013482:Superoxide Dismutase; D000096923:Frataxin; C027576:4-hydroxy-2-nonenal