Roles of glial cells in neuroinflammation and neurodegeneration

Abstract

A gap junction is the major intercellular channel that facilitates direct signaling between cytoplasmic compartments of adjacent cells by transferring various small molecules (approximately 1 kDa) and ions. A gap junction consists of a pair of hemichannels, each of which is a hexameric cluster of protein subunits named connexin. Besides the functional gap junction with the coupled hemichannels, the uncoupled “free” hemichannels also facilitate two‐way transfer of molecules between the cytosol and extracellular space. Both gap junctions and hemichannels form the neuron–glia network, and contribute to the maintenance of homeostasis by propagating signals and buffering against toxins in the central nervous system. In contrast, recent evidence has also shown that microglial glutamate from hemichannels induces neuronal damage, and death signals are propagated from damaged cells to neighboring cells through gap junctions, suggesting that gap junctions and hemichannels are involved in the initiation and amplification of neuroinflammation and neurodegeneration in the central nervous system. Understanding the precise pathological roles of gap junctions and .hemichannels might lead to a new therapeutic approach that could slow and halt the progression of various neurological disorders.