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
Joint Authors
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
Source
Oxidative Medicine and Cellular Longevity
Issue
Vol. 2020, Issue 2020 (31 Dec. 2020), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2020-04-23
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract 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.
American Psychological Association (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
Modern Language Association (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
American Medical Association (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
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-1204162