کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10143408 | 1646166 | 2018 | 37 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
LGK974, a PORCUPINE inhibitor, mitigates cytotoxicity in an in vitro model of Parkinson's disease by interfering with the WNT/β-CATENIN pathway
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
علوم محیط زیست
بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
Paraquat (PQ) as an herbicide has been demonstrated to impair dopaminergic (DAergic) neurons and highly correlate with the etiology of Parkinson's disease (PD). WNT/β-CATENIN signaling is known for the specification and neurogenesis of midbrain DAergic neurons and implicated as a therapeutic target in treating many diseases, such as cancer and degenerative diseases. LGK974, a WNT pathway inhibitor, is currently under clinical trial for patients with malignancies. Since the exact role of WNT/β-CATENIN signaling in mediating PD is undetermined, LGK974 was used to examine its effect on the PQ-induced cell model of PD. LGK974 attenuated PQ-induced apoptosis and released mitochondrial pro-poptotic molecules in human neuroblastoma SH-SY5Y cell. PQ increased the levels of β-CATENIN, non-phosphorylated (Ser33/37/Thr41) β-CATENIN, and phosphorylated glycogen synthase kinase (GSK)-3α/β. PQ also increased the nuclear translocation of β-CATENIN, which can be attenuated by LKG974. Furthermore, LGK974 attenuated the PQ-induced release of mitochondrial proapoptotic factors and WNT agonist 1-induced cell death. Taken together, we have shown for the first time that LGK974 mediated through the WNT/β-CATENIN pathway to prevent PQ-induced cell death.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology - Volume 410, 1 December 2018, Pages 65-72
Journal: Toxicology - Volume 410, 1 December 2018, Pages 65-72
نویسندگان
Jung-Mou Yang, Huei-Mei Huang, Jing-Jy Cheng, Chuen-Lin Huang, Yi-Chao Lee, Chun-Tang Chiou, Hung-Tse Huang, Nai-Kuei Huang, Ying-Chen Yang,