The central nervous system (CNS) depends on microglial proton channels to maintain cellular homeostasis, regulate pH balance, and modulate inflammatory responses. Dysregulation of these channels has been linked to a number of neuroinflammatory and neurodegenerative conditions, such as Alzheimer's disease, Parkinson's disease, and ischemic stroke. In this study, we used a systematic screening assay to find a novel modulator for microglial proton channels. A diverse chemical library was screened to determine its effects on proton channel activity in microglial cells, and our results show a promising lead compound that selectively modulates proton channel function without endangering cell viability. In this work, we used a systematic screening assay to find a novel modulator for microglial proton channels. The effects of a chemically varied small-molecule library on microglial cell proton channel function were evaluated through screening. Without endangering cell viability or producing cytotoxic effects, the most promising candidate chemical demonstrated strong and specific modulation of proton channel activity. The chemical successfully changed microglial activation states, decreased excessive proton flux, and impacted downstream signalling pathways linked to inflammation, according to additional electrophysiological and molecular investigations.
Hv1, Alzheimer's disease, cell culture
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