Electroacupuncture Alleviates Parkinson's Disease by Targeting HDAC/SIRT-mediated Deacetylation of 14-3-3

Zhaoqin Wang^1,2Handan Zheng^1,2Lingjie Li³Lulu Cao^1,2Lin Shen²宇 乔^1,2Yiyi Chen¹Luyi Wu¹Guona Li^1,2Huangan Wu^1,2*

• ¹Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China
• ²Shanghai Research Institute of Acupuncture and Meridian, Shanghai, China
• ³Shanghai Municipal Hospital of Traditional Chinese Medicine, Shanghai, China

Abstract Introduction: Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic neurons and the accumulation of pathological α-synuclein. Although current treatments can alleviate symptoms, they do not modify disease progression. Growing evidence implicates gut microbiota dysbiosis and aberrant protein acetylation in PD pathogenesis. Electroacupuncture (EA) has shown therapeutic potential in PD; however, its effects on protein acetylation remain unclear. Methods: A PD mouse model was established through MPTP induction and fecal microbiota transplantation (FMT) from PD patients. Mice received EA stimulation at Baihui (GV20) and Yanglingquan (GB34) acupoints for 14 days. Behavioral tests, immunohistochemistry, Western blot, qPCR, and 4D label-free acetyl proteomics were employed to assess motor function, neuronal integrity, protein expression, and acetylation profiles. Results: EA significantly improved motor coordination, enhanced sensorimotor function in the adhesive removal test, and increased open-field activity in PD mice. It attenuated the loss of tyrosine hydroxylase–positive neurons and decreased α-synuclein accumulation in the substantia nigra. Proteomic analysis revealed hyperacetylation of Ywhaq (14-3-3) in PD mice, which was reversed by EA. Mechanistically, EA upregulated the expression of deacetylases HDAC1/2/3 and SIRT1/2 at both protein and mRNA levels, restoring acetylation homeostasis. Conclusion: Electroacupuncture ameliorates behavioral and neuropathological phenotypes in a PD mouse model by restoring deacetylase expression and normalizing protein acetylation, particularly of 14-3-3. Our results underscore the therapeutic potential of EA and highlight acetylation modulation as a promising strategy for PD treatment.