Inhibition of the canonical Wnt pathway by Dickkopf-1 contributes to the neurodegeneration in 6-OHDA-lesioned rats.
Dickkopf-1 (Dkk1), an antagonist of the Wnt/β-catenin pathway, has been implicated in many neurodegenerative diseases. However, it's unknown whether Dkk1 is involved in the pathogenesis of Parkinson's disease. In this study, we discovered that Dkk1 was increased in 6-hydroxydopamin(6-OHDA)-lesioned rats. In the meanwhile, inhibition of the canonical Wnt signaling pathway, including the activation of glycogen synthase kinase-3β (GSK-3β) and decrease of β-catenin, was also found in 6-OHDA-lesioned rats. Treatment with rhDkk1 aggravated the dopaminergic neuron damage of the substantia nigra and the inhibition of the canonical Wnt signaling pathway in 6-OHDA-lesioned rats, while the above effects in these rats were abolished by pretreatment with LiCl, an inhibitor of GSK-3β, for consecutive 7 d. These data suggest that Dkk1 plays an important role in the etiology of PD models and it contributes to the neurodegeneration in 6-OHDA-lesioned rats via inhibition of the canonical Wnt pathway.
Department of Pharmacology, Tongji Medical College of Huazhong University of Science and Technology, Wuhan 430030, China.
Yaoyan
Y
Dun
Gang
G
Li
Yang
Y
Yang
Zhengguo
Z
Xiong
Mei
M
Feng
Min
M
Wang
Yuan
Y
Zhang
Jizhou
J
Xiang
Rong
R
Ma
D000818:Animals; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000473:pathology*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D016627:Oxidopamine; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D051381:Rats; D017208:Rats, Wistar; D011994:Recombinant Proteins / Q000494:pharmacology; D015398:Signal Transduction; D013378:Substantia Nigra / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051153:Wnt Proteins / Q000502:physiology*; D051176:beta Catenin / Q000378:metabolism
C501126:DKK1 protein, human; C531384:Dkk1 protein, rat; D036341:Intercellular Signaling Peptides and Proteins; D011994:Recombinant Proteins; D051153:Wnt Proteins; D051176:beta Catenin; D016627:Oxidopamine; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3