TFE3-Mediated Autophagy is Involved in Dopaminergic Neurodegeneration in Parkinson’s Disease

Impairment of autophagy has been strongly implicated in the progressive loss of nigral dopaminergic neurons in Parkinson’s disease (PD). Transcription factor E3 (TFE3), an MiTF/TFE family transcription factor, has been identified as a master regulator of the genes that are associated with lysosomal...

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Autores principales:	Xin He, Yue Xie, Qiongping Zheng, Zeyu Zhang, Shanshan Ma, Junyu Li, Mingtao Li, Qiaoying Huang
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	Parkinson’s disease dopaminergic neurons autophagy TFE3 MPTP Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/11ef0a83f7874ab7807e3565cf7d88de
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id	oai:doaj.org-article:11ef0a83f7874ab7807e3565cf7d88de
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spelling	oai:doaj.org-article:11ef0a83f7874ab7807e3565cf7d88de2021-12-01T14:01:27ZTFE3-Mediated Autophagy is Involved in Dopaminergic Neurodegeneration in Parkinson’s Disease2296-634X10.3389/fcell.2021.761773https://doaj.org/article/11ef0a83f7874ab7807e3565cf7d88de2021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fcell.2021.761773/fullhttps://doaj.org/toc/2296-634XImpairment of autophagy has been strongly implicated in the progressive loss of nigral dopaminergic neurons in Parkinson’s disease (PD). Transcription factor E3 (TFE3), an MiTF/TFE family transcription factor, has been identified as a master regulator of the genes that are associated with lysosomal biogenesis and autophagy. However, whether TFE3 is involved in parkinsonian neurodegeneration remains to be determined. In this study, we found decreased TFE3 expression in the nuclei of the dopaminergic neurons of postmortem human PD brains. Next, we demonstrated that TFE3 knockdown led to autophagy dysfunction and neurodegeneration of dopaminergic neurons in mice, implying that reduction of nuclear TFE3 may contribute to autophagy dysfunction-mediated cell death in PD. Further, we showed that enhancement of autophagy by TFE3 overexpression dramatically reversed autophagy downregulation and dopaminergic neurons loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. Taken together, these findings demonstrate that TFE3 plays an essential role in maintaining autophagy and the survival of dopaminergic neurons, suggesting TFE3 activation may serve as a promising strategy for PD therapy.Xin HeYue XieQiongping ZhengZeyu ZhangShanshan MaJunyu LiMingtao LiQiaoying HuangFrontiers Media S.A.articleParkinson’s diseasedopaminergic neuronsautophagyTFE3MPTPBiology (General)QH301-705.5ENFrontiers in Cell and Developmental Biology, Vol 9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Parkinson’s disease dopaminergic neurons autophagy TFE3 MPTP Biology (General) QH301-705.5
spellingShingle	Parkinson’s disease dopaminergic neurons autophagy TFE3 MPTP Biology (General) QH301-705.5 Xin He Yue Xie Qiongping Zheng Zeyu Zhang Shanshan Ma Junyu Li Mingtao Li Qiaoying Huang TFE3-Mediated Autophagy is Involved in Dopaminergic Neurodegeneration in Parkinson’s Disease
description	Impairment of autophagy has been strongly implicated in the progressive loss of nigral dopaminergic neurons in Parkinson’s disease (PD). Transcription factor E3 (TFE3), an MiTF/TFE family transcription factor, has been identified as a master regulator of the genes that are associated with lysosomal biogenesis and autophagy. However, whether TFE3 is involved in parkinsonian neurodegeneration remains to be determined. In this study, we found decreased TFE3 expression in the nuclei of the dopaminergic neurons of postmortem human PD brains. Next, we demonstrated that TFE3 knockdown led to autophagy dysfunction and neurodegeneration of dopaminergic neurons in mice, implying that reduction of nuclear TFE3 may contribute to autophagy dysfunction-mediated cell death in PD. Further, we showed that enhancement of autophagy by TFE3 overexpression dramatically reversed autophagy downregulation and dopaminergic neurons loss in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. Taken together, these findings demonstrate that TFE3 plays an essential role in maintaining autophagy and the survival of dopaminergic neurons, suggesting TFE3 activation may serve as a promising strategy for PD therapy.
format	article
author	Xin He Yue Xie Qiongping Zheng Zeyu Zhang Shanshan Ma Junyu Li Mingtao Li Qiaoying Huang
author_facet	Xin He Yue Xie Qiongping Zheng Zeyu Zhang Shanshan Ma Junyu Li Mingtao Li Qiaoying Huang
author_sort	Xin He
title	TFE3-Mediated Autophagy is Involved in Dopaminergic Neurodegeneration in Parkinson’s Disease
title_short	TFE3-Mediated Autophagy is Involved in Dopaminergic Neurodegeneration in Parkinson’s Disease
title_full	TFE3-Mediated Autophagy is Involved in Dopaminergic Neurodegeneration in Parkinson’s Disease
title_fullStr	TFE3-Mediated Autophagy is Involved in Dopaminergic Neurodegeneration in Parkinson’s Disease
title_full_unstemmed	TFE3-Mediated Autophagy is Involved in Dopaminergic Neurodegeneration in Parkinson’s Disease
title_sort	tfe3-mediated autophagy is involved in dopaminergic neurodegeneration in parkinson’s disease
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/11ef0a83f7874ab7807e3565cf7d88de
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TFE3-Mediated Autophagy is Involved in Dopaminergic Neurodegeneration in Parkinson’s Disease

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