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ZKSCAN3 affects the autophagy‑lysosome pathway through TFEB in Parkinson's disease

  • Authors:
    • Ming Yang
    • Shukai Lin
    • Baofei Sun
    • Wei Chen
    • Jian Liu
    • Minglei Chen
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China, Department of Neurosurgery, Sanya Central Hospital (Hainan Third People's Hospital), Sanya, Hainan 572000, P.R. China, Key Laboratory of Human Brain bank for Functions and Diseases of Department of Education of Guizhou Province, College of Basic Medical, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China, Department of Neurosurgery, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China, Department of Neurology, Sanya Central Hospital (Hainan Third People's Hospital), Sanya, Hainan 572000, P.R. China
    Copyright: © Yang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 74
    |
    Published online on: February 25, 2025
       https://doi.org/10.3892/br.2025.1952
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Abstract

The present study aimed to explore the effects of zinc finger with KRAB and SCAN domains 3 (ZKSCAN3)/transcription factor EB (TFEB) on autophagy‑lysosome pathway in Parkinson's disease (PD). SH‑SY5Y cells were treated with 6‑hydroxydopamine to establish a PD cell model. A ZKSCAN3 overexpression vector and short interfering (si)RNAs were also constructed. The TFEB overexpression vector was transfected into the cells with ZKSCAN3 siRNA and the TFEB siRNA was transfected into the cells with the ZKSCAN3 overexpression vector. Reverse transcription‑quantitative and western blotting were performed to detect the expression levels of Beclin‑1, LC3II/I, α‑synuclein and lysosomal‑associated membrane protein 1 (Lamp‑1). Lysosomes were labelled with LysoTracker Red and morphological changes in the lysosomes were detected by using laser confocal scanning microscopy. Transmission electron microscopy was used to observe changes in autophagosomes and lysosomes. Compared with those in the normal group, the model group presented decreases in the LC3B, ZKSCAN3, TFEB, Beclin‑1 and Lamp‑1 mRNA levels and increases in the LC3A, LC3II/I and α‑synuclein protein levels. ZKSCAN3 overexpression resulted in a decrease in Beclin‑1, LC3I mRNA, LC3 II/I protein and α‑synuclein levels, as well as an increase in LC3II mRNA levels. ZKSCAN3 interference resulted in an increase in LC3A mRNA, LC3 II/I protein, Beclin‑1, α‑synuclein mRNA and Lamp‑1 and a decrease in LC3B mRNA and α‑synuclein. TFEB reversed the effects of ZKSCAN3. The results of lysosome detection revealed that, compared with that of the normal group, the fluorescence intensity of the model group was lower. The fluorescence intensity of the ZKSCAN3 interference group and TFEB interference group was greater than that of the interference empty group. Compared with those in the overexpression empty group, the fluorescence intensity and number of lysosomes in the ZKSCAN3 overexpression group and the TFEB overexpression group were lower. In conclusion, ZKSCAN3 affected the occurrence and development of PD through the TFEB‑mediated autophagy‑lysosome pathway.
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Copy and paste a formatted citation
Spandidos Publications style
Yang M, Lin S, Sun B, Chen W, Liu J and Chen M: ZKSCAN3 affects the autophagy‑lysosome pathway through TFEB in Parkinson's disease. Biomed Rep 22: 74, 2025.
APA
Yang, M., Lin, S., Sun, B., Chen, W., Liu, J., & Chen, M. (2025). ZKSCAN3 affects the autophagy‑lysosome pathway through TFEB in Parkinson's disease. Biomedical Reports, 22, 74. https://doi.org/10.3892/br.2025.1952
MLA
Yang, M., Lin, S., Sun, B., Chen, W., Liu, J., Chen, M."ZKSCAN3 affects the autophagy‑lysosome pathway through TFEB in Parkinson's disease". Biomedical Reports 22.4 (2025): 74.
Chicago
Yang, M., Lin, S., Sun, B., Chen, W., Liu, J., Chen, M."ZKSCAN3 affects the autophagy‑lysosome pathway through TFEB in Parkinson's disease". Biomedical Reports 22, no. 4 (2025): 74. https://doi.org/10.3892/br.2025.1952
Copy and paste a formatted citation
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Spandidos Publications style
Yang M, Lin S, Sun B, Chen W, Liu J and Chen M: ZKSCAN3 affects the autophagy‑lysosome pathway through TFEB in Parkinson's disease. Biomed Rep 22: 74, 2025.
APA
Yang, M., Lin, S., Sun, B., Chen, W., Liu, J., & Chen, M. (2025). ZKSCAN3 affects the autophagy‑lysosome pathway through TFEB in Parkinson's disease. Biomedical Reports, 22, 74. https://doi.org/10.3892/br.2025.1952
MLA
Yang, M., Lin, S., Sun, B., Chen, W., Liu, J., Chen, M."ZKSCAN3 affects the autophagy‑lysosome pathway through TFEB in Parkinson's disease". Biomedical Reports 22.4 (2025): 74.
Chicago
Yang, M., Lin, S., Sun, B., Chen, W., Liu, J., Chen, M."ZKSCAN3 affects the autophagy‑lysosome pathway through TFEB in Parkinson's disease". Biomedical Reports 22, no. 4 (2025): 74. https://doi.org/10.3892/br.2025.1952
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