Parkinson's disease (PD) is a chronic and progressive neurodegenerative disorder, surpassed in prevalence only by Alzheimer's disease, typically affecting middle-aged and elderly individuals [1]. PD is characterized by the loss of function of dopaminergic neurons, resulting in a decrease in dopamine, a neurotransmitter that regulates movement. The main clinical manifestations are impaired autonomic motor regulation [2], though non-motor symptoms, including cognitive, neurological, and emotional disorders, may also develop as the disease advances [3]. In sporadic and hereditary PD, neuronal dysfunction is partly attributed to the destruction of various proteins involved in autophagy and lysosomal processing, which leads to the accumulation of misfolded proteins and ultimately to the death of dopamine neurons.

Autophagy plays an important role in PD pathogenesis. Abnormal autophagy and autophagosome accumulation have been observed in the brain tissues of PD patients [4]. Recent studies indicate that mitochondrial dysfunction and autophagy-lysosome dysfunction are key components of PD pathogenesis [5], [6], [7]. Furthermore, autophagy-lysosome dysfunction is associated with microglia-mediated neuroinflammation [8]. In neurons, excessive mitochondrial division produces excess reactive oxygen species (ROS), while oxidative stress aggravates the damage attributable to mitochondrial [9].

L-dopamine agonists are widely used for treating PD. However, long-term levodopa use is associated with significant complications and a lack of significant positive outcomes [10]. At present, complementary and alternative therapies are being increasingly used to manage PD. Acupuncture, which involves various techniques, such as manual acupuncture (MA), EA, moxibustion, and pressure points [11], has shown clinical benefits and minimal side effects, especially for treating movement disorders and other neurological conditions [12], [13]. Clinical evidence indicates EA modulates neurogenic dysfunction in stroke [14], and integrated with traditional techniques, enhances functional recovery and quality of life [13], [15]. Such clinical efficacy in CNS-related dysfunction underscores the rationale for EA application in PD [13], [16]. Acupuncture has neuroprotective, anti-neuroinflammatory, and anti-apoptotic effects in PD models [17], [18], [19]. Neuroinflammation and the impairment of neurotrophic signaling are pivotal factors in the progression of neurodegenerative diseases. Evidence indicates that modulating neuroinflammation and enhancing BDNF-TrkB signaling can effectively ameliorate cognitive deficits and neuronal damage in various central nervous system CNS disorders [20], [21], [22]. These pathways play a crucial role in maintaining neuronal survival and synaptic plasticity under pathological conditions. However, the specific mechanisms by which acupuncture alleviates motor disorders and protects dopaminergic neurons in PD require further investigation.

The 1-methyl-4-phenyl-1,2,3, 6-tetrahydropyridine (MPTP) animal model triggers the degeneration of the dopaminergic system, leading to the depletion of dopamine and its metabolites in the dorsal striatum, prefrontal cortex, and hippocampus [23]. We found that EA stimulation significantly improved the behavior of MPTP-induced PD mice while alleviating dopamine neuron damage and increasing the levels of dopamine (DA) and its metabolites. We hypothesized that this effect may be attributed to the regulatory effects of EA on neuronal oxidative stress and inflammatory factors. Mitochondria are crucial organelles that provide energy for neuron injury and repair. Excessive mitochondrial division leads to mitochondrial dysfunction, inhibition of the autophagy pathway, and exacerbation of neuronal injury and inflammation [24]. Here, our findings suggest that EA treatment is associated with promoted mitochondrial fusion and the restoration of autophagy-lysosome dysfunction, which potentially facilitates the clearance of damaged mitochondria and correlates with reduced levels of oxidative stress and neuroinflammation (Scheme 1).