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New Synthetic 3-Benzoyl-5-Hydroxy-2H-Chromen-2-One (LM-031) Inhibits Polyglutamine Aggregation and Promotes Neurite Outgrowth through Enhancement of CREB, NRF2, and Reduction of AMPKα in SCA17 Cell Models
المؤلفون المشاركون
Chen, Chiung-Mei
Lin, Te-Hsien
Wu, Yih-Ru
Chen, Wan-Ling
Yang, Shu-Ting
Yang, Shu-Mei
Lin, Wenwei
Chao, Chih-Ying
Lee-Chen, Guey-Jen
Chang, Kuo-Hsuan
المصدر
Oxidative Medicine and Cellular Longevity
العدد
المجلد 2020، العدد 2020 (31 ديسمبر/كانون الأول 2020)، ص ص. 1-17، 17ص.
الناشر
Hindawi Publishing Corporation
تاريخ النشر
2020-04-23
دولة النشر
مصر
عدد الصفحات
17
التخصصات الرئيسية
الملخص EN
Spinocerebellar ataxia type 17 (SCA17) is caused by a CAG/CAA expansion mutation encoding an expanded polyglutamine (polyQ) tract in TATA-box binding protein (TBP), a general transcription initiation factor.
Suppression of cAMP-responsive element binding protein- (CREB-) dependent transcription, impaired nuclear factor erythroid 2-related factor 2 (NRF2) signaling, and interaction of AMP-activated protein kinase (AMPK) with increased oxidative stress have been implicated to be involved in pathogenic mechanisms of polyQ-mediated diseases.
In this study, we demonstrated decreased pCREB and NRF2 and activated AMPK contributing to neurotoxicity in SCA17 SH-SY5Y cells.
We also showed that licochalcone A and the related in-house derivative compound 3-benzoyl-5-hydroxy-2H-chromen-2-one (LM-031) exhibited antiaggregation, antioxidative, antiapoptosis, and neuroprotective effects in TBP/Q79-GFP-expressing cell models.
LM-031 and licochalcone A exerted neuroprotective effects by upregulating pCREB and its downstream genes, BCL2 and GADD45B, and enhancing NRF2.
Furthermore, LM-031, but not licochalcone A, reduced activated AMPKα.
Knockdown of CREB and NRF2 and treatment of AICAR (5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside), an AMPK activator, attenuated the aggregation-inhibiting and neurite outgrowth promoting effects of LM-031 on TBP/Q79 SH-SY5Y cells.
The study results suggest the LM-031 as potential therapeutics for SCA17 and probable other polyQ diseases.
نمط استشهاد جمعية علماء النفس الأمريكية (APA)
Chen, Chiung-Mei& Chen, Wan-Ling& Yang, Shu-Ting& Lin, Te-Hsien& Yang, Shu-Mei& Lin, Wenwei…[et al.]. 2020. New Synthetic 3-Benzoyl-5-Hydroxy-2H-Chromen-2-One (LM-031) Inhibits Polyglutamine Aggregation and Promotes Neurite Outgrowth through Enhancement of CREB, NRF2, and Reduction of AMPKα in SCA17 Cell Models. Oxidative Medicine and Cellular Longevity،Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1204162
نمط استشهاد الجمعية الأمريكية للغات الحديثة (MLA)
Chen, Chiung-Mei…[et al.]. New Synthetic 3-Benzoyl-5-Hydroxy-2H-Chromen-2-One (LM-031) Inhibits Polyglutamine Aggregation and Promotes Neurite Outgrowth through Enhancement of CREB, NRF2, and Reduction of AMPKα in SCA17 Cell Models. Oxidative Medicine and Cellular Longevity No. 2020 (2020), pp.1-17.
https://search.emarefa.net/detail/BIM-1204162
نمط استشهاد الجمعية الطبية الأمريكية (AMA)
Chen, Chiung-Mei& Chen, Wan-Ling& Yang, Shu-Ting& Lin, Te-Hsien& Yang, Shu-Mei& Lin, Wenwei…[et al.]. New Synthetic 3-Benzoyl-5-Hydroxy-2H-Chromen-2-One (LM-031) Inhibits Polyglutamine Aggregation and Promotes Neurite Outgrowth through Enhancement of CREB, NRF2, and Reduction of AMPKα in SCA17 Cell Models. Oxidative Medicine and Cellular Longevity. 2020. Vol. 2020, no. 2020, pp.1-17.
https://search.emarefa.net/detail/BIM-1204162
نوع البيانات
مقالات
لغة النص
الإنجليزية
الملاحظات
Includes bibliographical references
رقم السجل
BIM-1204162
قاعدة معامل التأثير والاستشهادات المرجعية العربي "ارسيف Arcif"
أضخم قاعدة بيانات عربية للاستشهادات المرجعية للمجلات العلمية المحكمة الصادرة في العالم العربي
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