Front Cell Dev Biol. 2021 Nov 29
Xin He, Yue Xie, Qiongping Zheng, Zeyu Zhang, Shanshan Ma, Junyu Li, Mingtao Li, and Qiaoying Huang
Products used in the paper Details Operation
AAV vector packaging rAAV2/9-hSyn-EGFP-miR30a-shTfe3-WPRE (AAV-shTFE3) was used to target murine Tfe3 gene and rAAV2/9-hSyn-EGFP-miR30ashScramble-WPREs (AAV-shScr) was used as a control. The Tfe3 shRNA sequence was 5′-GCGACAGAAGAAAGACAATCA-3’. The scrambled shRNA sequence was 5′-CCTAAGGTTAAGTCGCCCTCG-3′, non-target in mice. All the viruses were generated and packaged by BrainVTA (Wuhan, China) and PackGene Biotech (Guangzhou, China). Request Quote

Research Field: CNS

Keywords: Parkinson’s disease, dopaminergic neurons, autophagy, TFE3, MPTP

AAV Serotype: rAAV2/9

Dose: The titer of all the viruses in this study was 1×10^12 gc/mL. The AAV viruses were delivered at 100 nl/min unilaterally into the right SN

Routes of Administration: stereotaxic administration

Targeted organ: Dopaminergic Neurons in brain

Animal or cell line strain: C57BL/6 mice


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.

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