Histone Deacetylase 4 Inhibition Reduces Rotenone-Induced Alpha-Synuclein Accumulation via Autophagy in SH-SY5Y Cells

doi:10.3390/brainsci13040670

科研成果详情

题名	Histone Deacetylase 4 Inhibition Reduces Rotenone-Induced Alpha-Synuclein Accumulation via Autophagy in SH-SY5Y Cells
作者	Wang, Luxi 1,2; Liu, Ling 2; Han, Chao 2; Jiang, Haiyang 2; Ma, Kai 2; Guo, Shiyi 2; Xia, Yun 2; Wan, Fang 2; Huang, Jinsha 2; Xiong, Nian 2; Wang, Tao 2
发表日期	2023-04
发表期刊	BRAIN SCIENCES 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Parkinson's disease histone deacetylases histone deacetylase inhibitor gene therapy neuroprotection Parkinson’s disease
其他关键词	CHAPERONE-MEDIATED AUTOPHAGY ; PARKINSONS-DISEASE ; MODELS ; DEATH ; NEURONS ; NEURODEGENERATION ; ACETYLATION ; ACTIVATION ; PROTECTS ; TARGET
摘要	(1) Background: Parkinson's disease (PD) is the most common movement disorder. Imbalanced protein homeostasis and alpha-syn aggregation are involved in PD pathogenesis. Autophagy is related to the occurrence and development of PD and can be regulated by histone deacetylases (HDACs). Various inhibitors of HDACs exert neuroprotective effects within in vitro and in vivo models of PD. HDAC4, a class II HDAC, colocalizes with alpha-synuclein and ubiquitin in Lewy bodies and also accumulates in the nuclei of dopaminergic neurons in PD models. (2) Methods: In the present study, the gene expression profile of HDACs from two previously reported datasets in the GEO database was analyzed, and the RNA levels of HDAC4 in brain tissues were compared between PD patients and healthy controls. In vitro, SH-SY5Y cells transfected with HDAC4 shRNA or pretreated with mc1568 were treated with 1 mu M of rotenone for 24 h. Then, the levels of alpha-syn, LC3, and p62 were detected using Western blot analysis and immunofluorescent staining, and cell viabilities were detected using Cell Counting Kit-8 (CCK-8). (3) Results: HDAC4 was highly expressed in PD substantia nigra and locus coeruleus. Mc1568, an inhibitor of HDAC4, decreased alpha-synuclein levels in rotenone-treated SH-SY5Y cells in a concentration-dependent manner and activated autophagy, which was impaired by rotenone. The knockdown of HDAC4 reversed rotenone-induced alpha-syn accumulation in SH-SY5Y cells and protected the neurons by enhancing autophagy. (4) Conclusions: HDAC4 is a potential therapeutic target for PD. The inhibition of HDAC4 by mc1568 or a gene block can reduce alpha-syn levels by regulating the autophagy process in PD. Mc1568 is a promising therapeutic agent for PD and other disorders related to alpha-syn accumulation.
资助项目	National Natural Science Foundation of China[81671260,81701258,81974201];Zhejiang Provincial Natural Science Foundation of China[LQ19H090011];Wenzhou Science and Technology Bureau Program[Y20180134];
出版者	MDPI
ISSN	2076-3425
EISSN	2076-3425
卷号	13 期号:4
DOI	10.3390/brainsci13040670
页数	13
WOS类目	Neurosciences
WOS研究方向	Neurosciences & Neurology
WOS记录号	WOS:000977692300001
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	37190635
SCOPUSEID	2-s2.0-85156240566
通讯作者地址	[Wang, Tao]Department of Neurology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China
Scopus学科分类	Neuroscience (all)
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/180144
专题	第一临床医学院（信息与工程学院）、附属第一医院_内科学_神经内科
通讯作者	Wang, Tao
作者单位	1.Department of Neurology,The First Affiliated Hospital of Wenzhou Medical University,Wenzhou,325000,China; 2.Department of Neurology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,430022,China
第一作者单位	第一临床医学院（信息与工程学院）、附属第一医院_内科学_神经内科
第一作者的第一单位	第一临床医学院（信息与工程学院）、附属第一医院_内科学_神经内科
推荐引用方式 GB/T 7714	Wang, Luxi,Liu, Ling,Han, Chao,et al. Histone Deacetylase 4 Inhibition Reduces Rotenone-Induced Alpha-Synuclein Accumulation via Autophagy in SH-SY5Y Cells[J]. BRAIN SCIENCES,2023,13(4).
APA	Wang, Luxi., Liu, Ling., Han, Chao., Jiang, Haiyang., Ma, Kai., ... & Wang, Tao. (2023). Histone Deacetylase 4 Inhibition Reduces Rotenone-Induced Alpha-Synuclein Accumulation via Autophagy in SH-SY5Y Cells. BRAIN SCIENCES, 13(4).
MLA	Wang, Luxi,et al."Histone Deacetylase 4 Inhibition Reduces Rotenone-Induced Alpha-Synuclein Accumulation via Autophagy in SH-SY5Y Cells".BRAIN SCIENCES 13.4(2023).