2. Academic Validation
  3. ZKSCAN3 affects the autophagy‑lysosome pathway through TFEB in Parkinson's disease

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

  • Biomed Rep. 2025 Feb 25;22(4):74. doi: 10.3892/br.2025.1952.
Ming Yang 1,  Shukai Lin 2,  Baofei Sun 3,  Wei Chen 4,  Jian Liu 4,  Minglei Chen 5
Affiliations

Affiliations

  • 1 Department of Neurosurgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China.
  • 2 Department of Neurosurgery, Sanya Central Hospital (Hainan Third People's Hospital), Sanya, Hainan 572000, P.R. China.
  • 3 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.
  • 4 Department of Neurosurgery, Guizhou Medical University, Guiyang, Guizhou 550025, P.R. China.
  • 5 Department of Neurology, Sanya Central Hospital (Hainan Third People's Hospital), Sanya, Hainan 572000, P.R. China.
PMID: 40083599 DOI: 10.3892/br.2025.1952
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.

Keywords

Parkinson's disease; autophagy; lysosome; zinc finger with KRAB and SCAN domains 3.

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