miR-302 Attenuates Mutant Huntingtin-Induced Cytotoxicity through Restoration of Autophagy and Insulin Sensitivity

doi:10.3390/ijms22168424

中山醫學大學機構典藏 CSMUIR > 中山醫學大學研究成果 > 期刊論文 > Item 310902500/23833

Please use this identifier to cite or link to this item: https://ir.csmu.edu.tw:8080/ir/handle/310902500/23833

Title:	miR-302 Attenuates Mutant Huntingtin-Induced Cytotoxicity through Restoration of Autophagy and Insulin Sensitivity
Authors:	Chang, CC;Tsou, SH;Chen, WJ;Ho, YJ;Hung, HC;Liu, GY;Singh, SK;Li, HH;Lin, CL
Keywords:	autophagy;Huntington's disease;insulin signaling;mitophagy;miR-302
Date:	2021
Issue Date:	2022-08-05T09:43:36Z (UTC)
Publisher:	MDPI
Abstract:	Huntington's disease (HD) is an autosomal-dominant brain disorder caused by mutant huntingtin (mHtt). Although the detailed mechanisms remain unclear, the mutational expansion of polyglutamine in mHtt is proposed to induce protein aggregates and neuronal toxicity. Previous studies have shown that the decreased insulin sensitivity is closely related to mHtt-associated impairments in HD patients. However, how mHtt interferes with insulin signaling in neurons is still unknown. In the present study, we used a HD cell model to demonstrate that the miR-302 cluster, an embryonic stem cell-specific polycistronic miRNA, is significantly downregulated in mHtt-Q74-overexpressing neuronal cells. On the contrary, restoration of miR-302 cluster was shown to attenuate mHtt-induced cytotoxicity by improving insulin sensitivity, leading to a reduction of mHtt aggregates through the enhancement of autophagy. In addition, miR-302 also promoted mitophagy and stimulated Sirt1/AMPK-PGC1 alpha pathway thereby preserving mitochondrial function. Taken together, these results highlight the potential role of miR-302 cluster in neuronal cells, and provide a novel mechanism for mHtt-impaired insulin signaling in the pathogenesis of HD.
URI:	http://dx.doi.org/10.3390/ijms22168424 https://www.webofscience.com/wos/woscc/full-record/WOS:000690609800001 https://ir.csmu.edu.tw:8080/handle/310902500/23833
Relation:	INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES ,2021,v22,issue 16
Appears in Collections:	[中山醫學大學研究成果] 期刊論文

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