Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons inside substantia nigra tissue and the synthesis of intracellular α-synuclein aggregates, known as Lewy bodies (Bloem et al., 2021; Eo et al., 2024). These pathological alterations contribute to the classic motor symptoms of PD, including bradykinesia, rigidity, and resting tremors, all of which severely impact the quality of life of affected individuals (Costa et al., 2023). Despite extensive investigations, the specific etiology of PD remains unclear, with both genetic and environmental factors playing roles in its development (Tysnes and Storstein, 2017). A significant contributor to neuronal damage and α-synuclein aggregation in PD is oxidative stress, which is the result of increased production of reactive oxygen species (ROS) (Zhu et al., 2024). Consequently, therapies aimed at mitigating oxidative stress and managing α-synuclein pathology have emerged as promising strategies to slow disease progression (Li et al., 2025).

The link between ROS and α-synuclein aggregation is central to the pathophysiology of sporadic PD (Zaltieri et al., 2015). Increased ROS levels can induce oxidative modifications in α-synuclein, triggering misfolding and aggregation into toxic oligomers and fibrils (Brás and Outeiro, 2021). These aggregates exacerbate oxidative stress by disrupting mitochondrial function and cellular homeostasis, thus establishing a feedback loop that accelerates neurodegeneration (Tofaris, 2022). Mitochondrial dysfunction, induced by oxidative stress, impairs ATP production, thereby increasing neuronal susceptibility to further damage, making it a promising therapeutic target (Thi Lai et al., 2024). This bidirectional interaction highlights the need to target both ROS and α-synuclein aggregation as part of a broader strategy to halt PD progression and safeguard vulnerable neuronal populations (Lv et al., 2023). ROS not only promotes protein aggregation but also activate neuroinflammatory pathways, further contributing to the pathogenesis of sporadic PD (Badanjak et al., 2021).

The growing recognition of magnetic field-based approaches as non-invasive neuromodulatory tools has been significantly shaped by work on repetitive transcranial magnetic stimulation (rTMS) in PD. Meta-analyses of randomized controlled trials have consistently demonstrated that rTMS produces significant improvements in motor symptoms in PD patients, with high-frequency stimulation over the primary motor cortex emerging as the most effective protocol and yielding significant effects on akinesia, rigidity, and tremor as assessed by the UPDRS-III (Li et al., 2022). A systematic review of rTMS and gait disturbances further established that high-frequency stimulation, particularly when combined with treadmill training, can alleviate freezing of gait and that the supplementary motor area (SMA) represents a promising target for patients with gait impairment (Nardone et al., 2020). Theta-burst stimulation protocols targeting the SMA over 14 consecutive days have produced rapid and long-lasting motor improvements in PD patients, with effects maintained up to 8 weeks after the end of treatment, highlighting the potential of accelerated stimulation schedules (Ji et al., 2021). Similarly, an accelerated cerebellar rTMS protocol applied over 5 consecutive days in a double-blind randomized sham-controlled trial produced encouraging motor improvements in PD patients in an outpatient setting, suggesting that condensed protocols may be both feasible and efficacious in clinical practice (Grobe-Einsler et al., 2024). Beyond motor symptoms, rTMS targeting the dorsolateral prefrontal cortex (DLPFC) using theta-burst stimulation has been shown to improve cognitive function in PD patients with mild cognitive impairment (Trung et al., 2019), and a large meta-analysis encompassing over 4000 participants has confirmed that NIBS, particularly rTMS, is effective in reducing depression and anxiety in PD (Zheng et al., 2022). At the preclinical level, gamma-rhythm low-field magnetic stimulation (LFMS), a variant of rTMS that delivers low-intensity, diffuse magnetic stimulation, has demonstrated neuroprotective effects in the MPTP mouse model of PD, improving motor function and preserving dopaminergic neurons in SNpc and striatal regions (Sekar et al., 2023). Collectively, these findings establish a strong rationale for investigating alternative magnetic field modalities,including the rotating magnetic field (RMF) approach examined in the present study,as novel therapeutic strategies for PD.

Rotating magnetic field (RMF) therapy has emerged as an innovative, noninvasive treatment approach for neurodegenerative diseases. It is postulated that RMF exerts neuroprotective effects by modulating oxidative stress, reducing inflammation, and preventing protein aggregation, making it a promising candidate for PD therapy (Han et al., 2023).

In the present study, we assessed the therapeutic potential of RMF in a well-established mouse model of sporadic PD. We hypothesized that RMF therapy would alleviate motor impairments and reduce the levels of neuropathological markers such as reactive oxygen species (ROS) and α-synuclein aggregates, providing neuroprotection. Through a combination of behavioral testing, biochemical evaluations, and immunohistochemical analyses, we aimed to elucidate the underlying mechanisms of RMF's therapeutic effects. Furthermore, we explored the potential of RMFs to modulate neuroinflammatory pathways and enhance neuronal survival, addressing key aspects of PD pathology. Our findings contribute to the growing body of evidence supporting noninvasive therapeutic strategies for PD and provide a deeper understanding of the role of RMFs in managing neurodegenerative diseases.