Harpagide Inhibits Microglial Activation and Protects Dopaminergic Neurons as Revealed by Nanoelectrode Amperometry†.

Main observation and conclusion: Parkinson's disease (PD) is one of the most common neurogenerative diseases (NDDs), characterized as less neurotransmitter release and loss of dopaminergic (DAergic) neurons with microglial inflammatory response as a key player. Natural product harpagide with anti‐inflammatory function is a potential therapeutic drug of PD, but its role towards microglial activation and inflammation‐mediated neuronal injury remained unsure. In this work, taking advantage of nanoelectrode amperometry with high temporal‐spatial resolution, we used nanowire electrodes (NWEs) to monitor intracellular reactive oxygen species (ROS) level and carbon fiber nanoelectrodes (CFNEs) to detect synaptic dopamine exocytosis, to explore the effect of harpagide in modulating microglial inflammatory reaction and protecting DAergic neurons in neuron‐microglia co‐culture system. The results indicate that harpagide inhibits microglia from activation induced by LPS/IFN‐γ and generation of ROS, therefore reduces inflammation‐mediated neural injury and maintains dopamine exocytosis function. These conclusions establish that harpagide possesses promising avenues for preventive or therapeutic interventions against PD and other NDDs. [ABSTRACT FROM AUTHOR]