Rotating Magnetic Field Therapy Induces System-Level Neuroprotection in A53T α-Synuclein Transgenic Mice Through...

Current therapeutic strategies for Parkinson's disease (PD) focus exclusively on symptomatic management without addressing underlying disease progression. Despite decades of research emphasizing the enhancement of the cellular defense pathway, disease-modifying treatments remain elusive. We evaluated rotating magnetic field (RMF) therapy in A53T transgenic mice harboring a familial PD-associated mutation. Transgenic and wild-type animals (n = 8 per group) received RMF treatment (4 Hz, 0.4 T, 2 h daily) for six months. Motor function, muscle strength, and neuropathological markers were assessed. Comprehensive transcriptomic and proteomic analyses were performed to elucidate the molecular mechanisms involved. Untreated A53T transgenic mice exhibited progressive motor decline (51% reduction in locomotor activity, 39% decrease in muscle strength) accompanied by the accumulation of pathological α-synuclein aggregates. RMF-treated transgenic mice demonstrated significant functional recovery, with 78% wild-type locomotor activity and 80% normal muscle strength, with a marked reduction in α-synuclein pathology. Molecular profiling revealed unexpected suppression of hyperactivated stress response pathways, including mTOR signaling, autophagy, and oxidative stress responses (NES = -2.05 to -2.65, FDR < 0.01), whereas metabolic defense mechanisms such as glutathione biosynthesis were increased (NES = 2.18, FDR < 0.001).These findings suggest that normalization of aberrant stress signaling through RMF therapy represents a novel disease-modifying strategy with potential applicability to other neurodegenerative disorders characterized by proteostasis dysfunction.