Research Progress In Acupuncture For Parkinson’s Disease: Insights Into The Mitochondrial Ferroptosis Pathway

Summary

This review systematically elucidates the molecular mechanisms of acupuncture in treating Parkinson's disease via the mitochondrial ferroptosis pathway, highlighting the intervention specificity of core acupoint combinations and electroacupuncture parameters.

Abstract

The pathogenesis of Parkinson's disease (PD) is highly complex, with mitochondrial ferroptosis—a novel regulated cell death modality—playing a critical role in dopaminergic neuronal degeneration. This review systematically elucidates the potential mechanisms of acupuncture in treating PD by modulating mitochondrial ferroptosis pathways, alongside analyzing the specificity of acupoint prescriptions and stimulation parameters. Databases, including PubMed and China National Knowledge Infrastructure (CNKI), were systematically searched for literature regarding acupuncture interventions in PD models and ferroptosis mechanisms. The analysis focused on acupuncture's regulation of mitochondrial iron overload, the System Xc⁻/glutathione (GSH)/glutathione peroxidase 4 (GPX4) antioxidant axis, and the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway. Acupuncture is proposed to mitigate mitochondrial ferroptosis through multidimensional synergistic mechanisms. First, it remodels iron metabolism by inhibiting transferrin receptor 1 (TFR1)/divalent metal transporter 1 (DMT1)-mediated iron uptake and upregulating ferritin heavy chain 1 (FTH1) to sequester iron harmlessly, thereby reducing the mitochondrial labile iron pool. Second, it may help restore antioxidant defenses by activating Nrf2 nuclear translocation, upregulating GPX4, and restoring the System Xc⁻/GSH pathway to scavenge lipid peroxides. Third, regarding intervention specificity, the Fengfu (GV16) and Taichong (LR3) combination primarily modulates neuroinflammation, whereas Baihui (GV20) penetration upregulates neurotrophic factors. Additionally, 2 Hz low-frequency electroacupuncture emerges as the optimal parameter for neuroprotection, while acupuncture also exerts systemic effects via synchronous brain-gut regulation. Acupuncture maintains mitochondrial homeostasis and inhibits neuronal ferroptosis by restoring the iron-lipid-antioxidant triangular balance. Future multi-omics and clinical translational research are required to optimize parameters and provide robust evidence for neuroprotective PD therapies.

Introduction

PD is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra pars compacta and the pathological aggregation of α-synuclein (α-syn). Its pathogenesis is highly complex, involving the intricate interplay of multiple dimensions, including oxidative stress, mitochondrial dysfunction, and neuroinflammation^1,2. Although current dopamine replacement therapies can alleviate motor symptoms to some extent, they fail to arrest the relentless progression of neuronal death. Furthermore, the clinical benefits of long-term medication are often limited by a....