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Adv."],"published-print":{"date-parts":[[2026,5,1]]},"abstract":"<jats:p>Traditional deep-brain stimulation via implanted electrodes can effectively treat neurological disorders, but surgical injury limits its clinical application. Here, we developed ultrasound-responsive piezoelectric nanoparticles for minimal-invasive and wireless neuromodulation. In the 6-OHDA\u2013induced Parkinson\u2019s disease (PD) mouse model, these nanoparticles are injected into the subthalamic nucleus (STN) of the mouse brain. After ultrasound stimulation for several days, the motor behavior, particularly gait abnormalities and nonmotor symptoms such as pain and anxiety, in PD mice is alleviated without detectable toxicity. The piezoelectric nanoparticles can activate the STN area of the mouse after ultrasound stimulation. Our results demonstrate that piezoelectric-mediated neuromodulation of the STN reverses motor deficits in PD by modulating neural signals, thereby protecting dopaminergic neurons and enhancing levels of the neurotransmitter dopamine. This process can rescue and mitigate mitochondrial dysfunction and neuroinflammation in the nigrostriatal pathway. Our approach enables STN neuronal activation with minimal invasiveness, offering a promising strategy for treating neurodegenerative diseases.<\/jats:p>","DOI":"10.1126\/sciadv.aec6955","type":"journal-article","created":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T17:59:01Z","timestamp":1777658341000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":1,"title":["Piezoelectric neuromodulation of the subthalamic nucleus ameliorates motor and nonmotor symptoms of Parkinson\u2019s disease"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-5605-6331","authenticated-orcid":true,"given":"Di","family":"Zhao","sequence":"first","affiliation":[{"name":"Institute of Brain Science and Disease, Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders, Qingdao University, Qingdao 266021, China."},{"name":"Department of Applied Physics, The Hong Kong Polytechnic University, Hong Kong 999077, P. 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