Microglial ion channels: Key players in non-cell autonomous neurodegeneration

Neuroinflammation is a critical pathophysiological hallmark of neurodegenerative disorders, including Alzheimer's disease (AD), Parkinson's disease (PD), and traumatic brain injury (TBI). Microglia, the first responders of the brain, are the drivers of this neuroinflammation. Microglial activation, leading to induction of pro-inflammatory factors, like Interleukin 1-β (IL-1β), Tumor necrosis factor-α (TNFα), nitrites, and others, have been shown to induce neurodegeneration. Non-steroidal anti-inflammatory drugs (NSAIDs) have been shown to reduce the risk of developing PD, but the mechanism underlying the microglial activation is still under active research. Recently, microglial ion channels have come to the forefront as potential drug targets in multiple neurodegenerative disorders, including AD and PD. Microglia expresses a variety of ion channels, including potassium channels, calcium channels, chloride channels, sodium channels, and proton channels. The diversity of channels present on microglia is responsible for the dynamic nature of these immune cells of the brain. These ion channels regulate microglial proliferation, chemotaxis, phagocytosis, antigen recognition and presentation, apoptosis, and cell signaling leading to inflammation, among other critical critical functions. Understanding the role of these ion channels and the signaling mechanism these channels regulate under pathological conditions is an active area of research. This review will be focusing on the roles of different microglial ion channels, and their potential role in regulating microglial functions in neurodegenerative disorders.