TFEB Biology and Agonists at a Glance

Chen, Mingyue; Dai, Yashuang; Liu, Siyu; Fan, Yuxin; Ding, Zongxian; Li, Dan

doi:10.3390/cells10020333

Cited by 48 publications

(28 citation statements)

References 96 publications

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“…In addition, a recent report indicated that TFE3 overexpression augments autophagy flux and ameliorates ER stress-induced apoptosis in neurons following spinal cord injury ( Zhou et al, 2020 ), supporting the notion that TFE3 activation could be neuroprotective. Efforts have been made to develop TFEB agonists to enhance autophagy in neurodegenerative disease ( Chen et al, 2021 ), and our results suggest that TFE3 could also be a promising drug target.…”

Section: Discussionmentioning

confidence: 70%

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

Xie

Zheng

et al. 2021

Front. Cell Dev. Biol.

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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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Section: Discussionmentioning

confidence: 70%

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

Xie

Zheng

et al. 2021

Front. Cell Dev. Biol.

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“…This motif, termed coordinated lysosomal expression and regulation (CLEAR) element, consists of an E-box (CANNTG) identified by MIT/TFE family transcription factors (e.g., TFEB and TFE3) 26 . TFEB promotes transcription and expression of its target genes by specifically binding to the distinct CLEAR motif in the target promoter 26 , which increases the biogenesis of lysosomes and improves their degradation ability 27 .…”

Section: New Understanding Of Lysosomal Function and Regulation Recent Findings On Lysosomal Functionmentioning

confidence: 99%

Relationship between lysosomal dyshomeostasis and progression of diabetic kidney disease

Zhang

et al. 2021

Cell Death Dis

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Lysosomes are organelles involved in cell metabolism, waste degradation, and cellular material circulation. They play a key role in the maintenance of cellular physiological homeostasis. Compared with the lysosomal content of other organs, that of the kidney is abundant, and lysosomal abnormalities are associated with the occurrence and development of certain renal diseases. Lysosomal structure and function in intrinsic renal cells are impaired in diabetic kidney disease (DKD). Promoting lysosomal biosynthesis and/or restoring lysosomal function can repair damaged podocytes and proximal tubular epithelial cells, and delay the progression of DKD. Lysosomal homeostasis maintenance may be advantageous in alleviating DKD. Here, we systematically reviewed the latest advances in the relationship between lysosomal dyshomeostasis and progression of DKD based on recent literature to further elucidate the mechanism of renal injury in diabetes mellitus and to highlight the application potential of lysosomal homeostasis maintenance as a new prevention and treatment strategy for DKD. However, research on screening effective interventions for lysosomal dyshomeostasis is still in its infancy, and thus should be the focus of future research studies. The screening out of cell-specific lysosomal function regulation targets according to the different stages of DKD, so as to realize the controllable targeted regulation of cell lysosomal function during DKD, is the key to the successful clinical development of this therapeutic strategy.

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“…The overexpression of TFEB increases the autophagy levels in major organs and protects against LPS induce acute lung injury (Liu et al, 2019) or inflammatory liver injury and pancreatitis (Chao et al, 2018;Wang et al, 2019). Moreover, the pharmacological activation of TFEB by extrinsic stimuli or intrinsic signaling molecules is known to protect against septic liver injury, acute kidney injury (Li D. et al, 2021), and cardiac dysfunction (Unuma et al, 2013).…”

Section: Organ Protectionmentioning

confidence: 99%

“…Although the overexpression of TFEB has been investigated in cells and experimental rodents to evaluate its ability to activate the ALP, the pharmacological modulation of TFEB by means of activators is more desirable for therapeutic applications in the short term. For example, recent research has reported that small molecules and biomacromolecules (e.g., microRNAs (miRNA), polysaccharides and peptides) can modulate the ALP by activating TFEB (Xu H. et al, 2020;Chen et al, 2021). These activators have been categorized according to the pharmacological mechanisms by which they regulate TFEB.…”

Section: The Pharmacological Application Of Tfeb Activators As a Therapeutic Option For Sepsismentioning

confidence: 99%

TFEB Dependent Autophagy-Lysosomal Pathway: An Emerging Pharmacological Target in Sepsis

Liu

Zheng

et al. 2021

Front. Pharmacol.

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Sepsis is a life-threatening syndrome induced by aberrant host response towards infection. The autophagy-lysosomal pathway (ALP) plays a fundamental role in maintaining cellular homeostasis and conferring organ protection. However, this pathway is often impaired in sepsis, resulting in dysregulated host response and organ dysfunction. Transcription factor EB (TFEB) is a master modulator of the ALP. TFEB promotes both autophagy and lysosomal biogenesis via transcriptional regulation of target genes bearing the coordinated lysosomal expression and regulation (CLEAR) motif. Recently, increasing evidences have linked TFEB and the TFEB dependent ALP with pathogenetic mechanisms and therapeutic implications in sepsis. Therefore, this review describes the existed knowledge about the mechanisms of TFEB activation in regulating the ALP and the evidences of their protection against sepsis, such as immune modulation and organ protection. In addition, TFEB activators with diversified pharmacological targets are summarized, along with recent advances of their potential therapeutic applications in treating sepsis.

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TFEB Biology and Agonists at a Glance

Cited by 48 publications

References 96 publications

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

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

Relationship between lysosomal dyshomeostasis and progression of diabetic kidney disease

TFEB Dependent Autophagy-Lysosomal Pathway: An Emerging Pharmacological Target in Sepsis

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