The paradoxical role of zinc on microglia

Zinc is an essential trace element for humans, and its homeostasis is essential for the health of the central nervous system. Microglia, the resident immune cells in the central nervous system, play the roles of sustaining, nourishing, and immune surveillance. Microglia are sensitive to microenvironment changes and are easily activated to M1 phenotype to enhance disease progression or the M2 phenotype to improve peripheral nerves injury repair. Zinc is requisite for microglial activation, However, the cytotoxicity outcome of zinc against microglia, the activated microglia phenotype, and activated microglia function are ambiguous. Herein, we have reviewed the neurological function of zinc and microglia, particularly the ambiguous role of zinc on microglia. We also pay attention to the role of zinc homeostasis on microglial function within the central nervous system disease. Finally, we observe the relationship between zinc and microglia, attempting to design new therapeutic measures against major nervous system disorders.