2. Academic Validation
  3. PRMT5 Aggravates Parkinson's Disease Progression Through the Inhibition of Neuronal Autophagy Through DKK1

PRMT5 Aggravates Parkinson's Disease Progression Through the Inhibition of Neuronal Autophagy Through DKK1

  • Neurochem Res. 2025 Dec 11;51(1):12. doi: 10.1007/s11064-025-04625-2.
Houjun Zhou 1 2,  Hao Fan 3,  Hui Bian 4,  Yanghong Zou 1 2,  Ailan Pang 2 5,  Xin Geng 6 7
Affiliations

Affiliations

  • 1 The Second Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China.
  • 2 NHC Key Lab of Drug Addiction Medicine (Kunming Medical University), Kunming, 650500, Yunnan, China.
  • 3 Department of Biochemistry and Molecular Biology, School of Basic Medicine, Kunming Medical University, Kunming, 650500, Yunnan, China.
  • 4 Department of Physiology, Faculty of Basic Medical Science, Kunming Medical University, Kunming, 650500, Yunnan, China.
  • 5 Department of Neurology, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China.
  • 6 The Second Department of Neurosurgery, The First Affiliated Hospital of Kunming Medical University, Kunming, 650032, Yunnan, China. [email protected].
  • 7 NHC Key Lab of Drug Addiction Medicine (Kunming Medical University), Kunming, 650500, Yunnan, China. [email protected].
PMID: 41379372 DOI: 10.1007/s11064-025-04625-2
Abstract

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide and severely affects the physical and mental health of patients. The protein arginine methyltransferase 5 (PRMT5) has been shown to be associated with neuronal degeneration in PD, but its specific mechanism of mediating PD remains unclear. The purpose of this study was to investigate the role of PRMT5 in PD and its potential mechanism. PD models in rats and MN9D cells were induced by 6-hydroxydopamine (6-OHDA). Key genes and proteins were identified through real-time quantitative polymerase chain reaction (RT‒qPCR), Western blotting, and immunofluorescence staining; Apoptosis levels were measured using flow cytometry; autophagosome formation was observed via monodansylcadaverine (MDC) staining; and neuronal damage in PD rats was evaluated using hematoxylin‒eosin (H&E) and Nissl staining. In this study, we found that PRMT5 levels were elevated in the peripheral blood of PD patients and in 6-OHDA-induced rat brain tissue and MN9D cells and that the expression of PRMT5 was positively correlated with the level of α-Syn. After PRMT5 was knocked down, α-Syn levels in PD rats decreased, neuronal damage was inhibited, and motor disorders improved. In addition, knockdown of PRMT5 promoted 6-OHDA-induced MN9D cell proliferation, inhibited Apoptosis, and upregulated Autophagy. Mechanistically, PRMT5 inhibits the activation of the Wnt/β-catenin signaling pathway through H3R8me2s modification to stabilize the expression of DKK1, thus inhibiting neuronal Autophagy and promoting the development of PD. Our study suggests that PRMT5 may be a potential intervention target for improving PD progression.

Keywords

Autophagy; DKK1; PRMT5; Parkinson’s disease; Wnt/β-catenin signaling pathway.

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