Figure 1.

Phenotype change of microglia in neurodegenerative disorders. In response to neuronal damage, signals mediated from neurons, such as neurotransmitter or amyloid-β (Aβ), act as “on” or “off” signals for microglial activation. In response to “on” signals, there can be the alteration of its phenotype into two distinct states—M1: classically active state and M2: alternative active state. In the M1 state, microglia express iNOS and MHC II, activating the NF-κB pathway to produce several pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), IL-1β, IL-6, IL-12 and IL-23, and generate ROS and NO, which subsequently induce immune stimulation, neuroinflammation, block of axonal remodeling and prevent neurogenesis. Unlike the M1 active state, the M2 or alternative active state mediate neuroprotection through Aβ phagocytosis and clearance, modulate neuronal regeneration, and releases arginase 1 (Arg1) for tissue remodeling, wound healing and debris clearance through releasing M2 markers, Arg1, found in inflammatory zone 1 (FIZZ1), chitinase-like protein 1 (Ym1), triggering receptor also expressed on myeloid cells (TREM), CD163, CD301, CD206 and IL-1 receptor antagonist (IL-1Ra) and also expressing other markers, such as scavenger receptor class A1 (SR-A1), scavenger receptor class B1 (SR-B1) and sphingosine kinase (Sphk).