Accurate Neurotransmitter Release by Ultrasound-Responsive Nanomaterials for Alleviating L-DOPA-Induced Dyskinesia in Parkinson's Disease.

Functional nanomaterials show great promise in next-generation targeted non-genetic neuromodulation and on-demand neurotransmitter release with superior spatiotemporal accuracy. L-DOPA-induced dyskinesia (LID) is a common complication during the treatment process of Parkinson's disease. Dysfunction in the dynamics of dopamine release plays a pivotal role in the disease. A strategy for LID treatment by using ultrasound-responsive functional nanomaterials for controlled release of nitric oxide is proposed, which can activate the nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) signaling pathway. This alleviates the abnormal synaptic plasticity caused by excessive and pulsatile dopamine, and diminishes hypersensitivity of the D1 dopamine receptors, thereby reducing the behavioral disorders associated with LID. These findings offer a novel perspective for therapy of neurodegenerative diseases.