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 D 1 dopamine receptors, thereby reducing the behavioral disorders associated with LID. These findings offer a novel perspective for therapy of neurodegenerative diseases.