Fig. 8

Schematic representation of microglial involvement in the ALS-CSF/CHIT-1-induced neurotoxicity. Microglial activation marks the early event of SALS pathology in response to the inflammatory trigger through ALS-CSF/CHIT-1 exposure. It results in the vicious cycle leading to activation/overactivation of microglial cells, followed by morphological and functional transformation of the microglial cells to encourage neuroinflammation. The activation leads to a push-forward mechanism, encouraging the overproduction of pro-inflammatory cytokines as an early event, subsequently leading to the production of PGE2, ROS, NO, and glutamate, while downregulating beneficial trophic factors and anti-inflammatory factors. These events may lead to motor neuron degeneration through interlinked pathways. MGC multinucleated giant cell MV shedding = activated microglia engaged in shedding microvesicle-like structures; cytorrhexis = cytoplasmic fragmentation resulting from microglial death due to overactivation