A Small Natural Molecule S3 Protects Retinal Ganglion Cells and Promotes Parkin-Mediated Mitophagy against Excitotoxicity

doi:10.3390/molecules27154957

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	A Small Natural Molecule S3 Protects Retinal Ganglion Cells and Promotes Parkin-Mediated Mitophagy against Excitotoxicity
	Zhuang, Dongli; Zhang, Rong; Liu, Haiyang; Dai, Yi
	2022
发表期刊	MOLECULES
卷号	27 期号:15 页码:4957
摘要	Glutamate excitotoxicity may contribute to retinal ganglion cell (RGC) degeneration in glaucoma and other optic neuropathies, leading to irreversible blindness. Growing evidence has linked impaired mitochondrial quality control with RGCs degeneration, while parkin, an E3 ubiquitin ligase, has proved to be protective and promotes mitophagy in RGCs against excitotoxicity. The purpose of this study was to explore whether a small molecule S3 could modulate parkin-mediated mitophagy and has therapeutic potential for RGCs. The results showed that as an inhibitor of deubiquitinase USP30, S3 protected cultured RGCs and improved mitochondrial health against NMDA-induced excitotoxicity. Administration of S3 promoted the parkin expression and its downstream mitophagy-related proteins in RGCs. An upregulated ubiquitination level of Mfn2 and protein level of OPA1 were also observed in S3-treated RGCs, while parkin knockdown resulted in a major loss of the protective effect of S3 on RGCs under excitotoxicity. These findings demonstrated that S3 promoted RGC survival mainly through enhancing parkin-mediated mitophagy against excitotoxicity. The neuroprotective value of S3 in glaucoma and other optic neuropathies deserves further investigation.
关键词	excitotoxicity retinal ganglion cells 15-oxospiramilactone mitophagy parkin MITOCHONDRIAL USP30
DOI	10.3390/molecules27154957
收录类别	SCI
WOS记录号	WOS:000839828500001
引用统计
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/74738
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Zhuang, Dongli,Zhang, Rong,Liu, Haiyang,et al. A Small Natural Molecule S3 Protects Retinal Ganglion Cells and Promotes Parkin-Mediated Mitophagy against Excitotoxicity[J]. MOLECULES,2022,27(15):4957.
APA	Zhuang, Dongli,Zhang, Rong,Liu, Haiyang,&Dai, Yi.(2022).A Small Natural Molecule S3 Protects Retinal Ganglion Cells and Promotes Parkin-Mediated Mitophagy against Excitotoxicity.MOLECULES,27(15),4957.
MLA	Zhuang, Dongli,et al."A Small Natural Molecule S3 Protects Retinal Ganglion Cells and Promotes Parkin-Mediated Mitophagy against Excitotoxicity".MOLECULES 27.15(2022):4957.

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