Novel Insight into Functions of Transcription Factor EB (TFEB) in Alzheimer’s Disease and Parkinson’s Disease

Yang, Jing; Zhang, Wei; Zhang, Shugeng; Iyaswamy, Ashok; Sun, Jichao; Wang, Jigang; Yang, Chonglin

doi:10.14336/ad.2022.0927

Cited by 11 publications

(8 citation statements)

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“…The upstream pathways that lead to the dephosphorylation of TFEB and induce its nuclear translocation include the ERK2, mTOR, GSK3β, PKC, and calcineurin pathways . We investigated the alterations of these upstream signaling pathways of TFEB following exposure to PEG–CZNPs.…”

Section: Resultsmentioning

confidence: 99%

“…The upstream pathways that lead to the dephosphorylation of TFEB and induce its nuclear translocation include the ERK2, mTOR, GSK3β, PKC, and calcineurin pathways. 31 We investigated the alterations of these upstream signaling pathways of TFEB following exposure to PEG−CZNPs. Among the pathways examined, there was a notable increase in the phosphorylation of Akt (p-Akt) and GSK3β at serine 9 (p-Ser 9 -GSK3β) upon exposure to PEG−CZNPs, indicative of the inactive stage of GSK3β (Figure 3a).…”

Section: Peg−cznps Promote Tfeb Nuclear Translocation Through Akt/gsk3βmentioning

confidence: 99%

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PEG-Capped Ceria–Zirconia Nanoparticles Improved Renal Fibrosis In Cellular and Animal Models of Fabry Disease

Kim,

Hong,

et al. 2024

ACS Appl. Nano Mater.

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Fabry disease (FD) is an X-linked hereditary disorder that results in the malfunction of α-galactosidase A (αGLA), leading to the accumulation of globotriaosylceramide (GB3) in cells and causing organ damage. This condition induces several pathological intracellular signaling pathways, with the dysfunction in autophagy being a crucial component. Phospholipid−polyethylene glycol-capped Ceria−Zirconia antioxidant nanoparticles (PEG−CZNPs) have been reported to enhance autophagy flux. This study aims to assess the mechanisms of action of PEG−CZNPs in autophagy regulation and examine their effects on chronic kidney injury in cellular and animal models of FD. A stable cellular model of FD was successfully created through the shRNA transfection of αGLA. PEG−CZNPs were found to enhance autophagy flux by translocating Transcription factor EB (TFEB) to the nucleus. To demonstrate TFEB's importance in autophagy flux by PEG−CZNPs, HK-2 cells were transfected with siTFEB. Autophagy flux significantly decreased after the knockdown of TFEB, despite PEG−CZNPs treatment. We next assessed the upper signaling pathway of TFEB by PEG−CZNPs. TFEB dephosphorylation was significantly influenced by the Akt/GSK3ß signaling pathway in response to PEG−CZNPs. PEG−CZNPs successfully reduced intracellular GB3 accumulation and decreased fibrous markers such as α-smooth muscle actin (αSMA), collagen type IV (ColIV), and matrix metallopeptidase 9 (MMP9) expression in the cellular model of FD. To evaluate the impact of PEG−CZNPs on kidney injury in a mouse model of FD, saline or PEG−CZNPs (10 mg/kg/day) were administered intraperitoneally twice per week for 24 or 48 weeks, starting at the age of 4 weeks. PEG−CZNPs significantly reduced both GB3 accumulation and αSMA expression in the kidneys. In conclusion, these results suggest that PEG− CZNPs promote autophagy flux through the Akt/GSK3β-TFEB signaling pathway and demonstrate a beneficial effect on kidney fibrosis and intracellular GB3 reduction in cellular and animal models of FD. These results provide valuable insights into potential therapeutics for FD.

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Section: Resultsmentioning

confidence: 99%

Section: Peg−cznps Promote Tfeb Nuclear Translocation Through Akt/gsk3βmentioning

confidence: 99%

PEG-Capped Ceria–Zirconia Nanoparticles Improved Renal Fibrosis In Cellular and Animal Models of Fabry Disease

Kim,

Hong,

et al. 2024

ACS Appl. Nano Mater.

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“…Decades of rigorous research have significantly enhanced our understanding of their pathophysiology. Recent reviews have summarized advances in the dynamics of the extracellular matrix and the regulation of intracellular transcription factors [ 129 , 130 ]. A growing body of research has shifted focus toward the role of neuroinflammation, providing novel insights that could potentially impede or inhibit the progression of such age-related brain disorders [ 131 , 132 ].…”

Section: Discussionmentioning

confidence: 99%

Mesenchymal Stem Cells-based Cell-free Therapy Targeting Neuroinflammation

Xu,

Wang,

et al. 2023

Aging and disease

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Emerging from several decades of extensive research, key genetic elements and biochemical mechanisms implicated in neuroinflammation have been delineated, contributing substantially to our understanding of neurodegenerative diseases (NDDs). In this minireview, we discuss data predominantly from the past three years, highlighting the pivotal roles and mechanisms of the two principal cell types implicated in neuroinflammation. The review also underscores the extended process of peripheral inflammation that predates symptomatic onset, the critical influence of neuroinflammation, and their dynamic interplay in the pathogenesis of NDDs. Confronting these complex challenges, we introduce compelling evidence supporting the use of mesenchymal stem cell-based cell-free therapy. This therapeutic strategy includes the regulation of microglia and astrocytes, modulation of peripheral nerve cell inflammation, and targeted anti-inflammatory interventions specifically designed for NDDs, while also discussing engineering and safety considerations. This innovative therapeutic approach intricately modulates the immune system across the peripheral and nervous systems, with an emphasis on achieving superior penetration and targeted delivery. The insights offered by this review have significant implications for the better understanding and management of neuroinflammation.

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“…Strategies targeting autophagylysosome pathways and the development of therapies to enhance lysosomal biogenesis and autophagy may offer promising avenues for discovering disease-modifying treatments for neurodegenerative disorders. 45…”

Section: F I G U R E 1 Overview Of Ncrnas Biogenesis and Functionsmentioning

confidence: 99%

Autophagy‐associated non‐coding RNAs: Unraveling their impact on Parkinson's disease pathogenesis

Hussain,

Moglad,

Afzal

et al. 2024

CNS Neurosci Ther

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BackgroundParkinson's disease (PD) is a degenerative neurological condition marked by the gradual loss of dopaminergic neurons in the substantia nigra pars compacta. The precise etiology of PD remains unclear, but emerging evidence suggests a significant role for disrupted autophagy—a crucial cellular process for maintaining protein and organelle integrity.MethodsThis review focuses on the role of non‐coding RNAs (ncRNAs) in modulating autophagy in PD. We conducted a comprehensive review of recent studies to explore how ncRNAs influence autophagy and contribute to PD pathophysiology. Special attention was given to the examination of ncRNAs' regulatory impacts in various PD models and patient samples.ResultsFindings reveal that ncRNAs are pivotal in regulating key processes associated with PD progression, including autophagy, α‐synuclein aggregation, mitochondrial dysfunction, and neuroinflammation. Dysregulation of specific ncRNAs appears to be closely linked to these pathogenic processes.ConclusionncRNAs hold significant therapeutic potential for addressing autophagy‐related mechanisms in PD. The review highlights innovative therapeutic strategies targeting autophagy‐related ncRNAs and discusses the challenges and prospective directions for developing ncRNA‐based therapies in clinical practice. The insights from this study underline the importance of ncRNAs in the molecular landscape of PD and their potential in novel treatment approaches.

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Novel Insight into Functions of Transcription Factor EB (TFEB) in Alzheimer’s Disease and Parkinson’s Disease

Cited by 11 publications

References 163 publications

PEG-Capped Ceria–Zirconia Nanoparticles Improved Renal Fibrosis In Cellular and Animal Models of Fabry Disease

PEG-Capped Ceria–Zirconia Nanoparticles Improved Renal Fibrosis In Cellular and Animal Models of Fabry Disease

Mesenchymal Stem Cells-based Cell-free Therapy Targeting Neuroinflammation

Autophagy‐associated non‐coding RNAs: Unraveling their impact on Parkinson's disease pathogenesis

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