Xu Tian, Zhang Li, Lu Xiaoxiao, Ji Wei, Chen Kaidong
School of Environmental Science and Engineering, Wuxi University, Wuxi, 214105, China.
Department of Neurology, The Affiliated Wuxi People's Hospital of Nanjing Medical University, Wuxi People's Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, China.
Neurosci Bull. 2025 May 29. doi: 10.1007/s12264-025-01420-5.
Parkinson's disease (PD) is a neurodegenerative disorder characterized by the aggregation of α-synuclein (α-syn) and dysregulated synaptic vesicle (SV) recycling. Emerging evidence suggests that ferroptosis is the target of PD therapy. However, the identification of effective anti-ferroptosis treatments remains elusive. This study explores the therapeutic potential of low-intensity ultrasound (US) in modulating SV recycling and anti-ferroptosis in cellular and animal models of PD. We demonstrate that optimized US stimulation (610 kHz, 0.2 W/cm) activates Piezo1 channel-mediated fast endophilin-mediated endocytosis, which promotes SV recycling and synaptic function, presenting with increased frequency and amplitude of both spontaneous excitatory synaptic currents and miniature excitatory postsynaptic currents. Repaired SV recycling in turn reduces the accumulation of α-syn expression and ferroptotic cell death. These findings support the potential of noninvasive ultrasonic neuromodulation as a therapeutic strategy for PD and lead to meaningful health outcomes for the aging population.
帕金森病（PD）是一种神经退行性疾病，其特征在于α-突触核蛋白（α-syn）的聚集和突触小泡（SV）循环失调。新出现的证据表明，铁死亡是PD治疗的靶点。然而，有效的抗铁死亡治疗方法仍难以确定。本研究探讨了低强度超声（US）在调节PD细胞和动物模型中SV循环及抗铁死亡方面的治疗潜力。我们证明，优化的超声刺激（610 kHz，0.2 W/cm）可激活Piezo1通道介导的、内吞蛋白介导的快速内吞作用，从而促进SV循环和突触功能，表现为自发性兴奋性突触电流和微小兴奋性突触后电流的频率和幅度增加。修复的SV循环反过来减少了α-syn表达的积累和铁死亡细胞死亡。这些发现支持了非侵入性超声神经调节作为PD治疗策略的潜力，并为老年人群带来有意义的健康结果。
