Table 1.

Summary of protective and detrimental pathways of microglial signaling.

	Mediated by	Function	Effect			References
			Microglia activation	Inflammation	Neurodegeneration
Protective microglia pathways	TGF-β via SMAD signaling	Neuroprotection, promote a quiescent state in microglia	↓	↓	↓	Abutbul et al. (2012)
	BDNF through JAK-STAT3 pathway	Neurotrophic	=	↓	↓	Zamanian et al. (2012) and Parkhurst et al. (2013)
	GDNF	Inhibition of microglia	↓	↓	↓	Rocha et al. (2012)
	NGF and NT-3 via p75	Downregulation of microglial activity	↓	=	=	Sobrado-Calvo et al. (2007) and Cragnolini et al. (2009)
	CD200-CD200R	Maintain microglia in a quiescent state	↓	↓	↓	Hernangómez et al. (2012); Shrivastava et al. (2012) and Oria et al. (2018)
	ORM2-CCR5 block CXCL4-CCR5	Inhibition of microglia	↓	↓	↓	Jo et al. (2017)
	TNF-TNFR2	Anti-inflammatory and neuroprotective	↑ anti-inflammatory cytokines	↓	=	Veroni et al. (2010) and Gao et al. (2017)
Detrimental microglia pathways	TNF-TNFR1	Microglia activation and neurotoxicity	↑	↑	↑ TNFR1-mediated neuronal loss	Fontaine et al. (2002)
	MD-1 (Ly86) protein	Innate immunity mediator	↑ increased proliferation	↑ chemokines CXCL10 and CCL2 production	↑	Jordão et al. (2019)
	IL-33 astrocytic expression	Pro-inflammatory	↑ chemokines expression	↑ recruitment of infiltrating macrophages in CNS	↑	Fairlie-Clarke et al. (2018)
	TLRs signaling	Pro-inflammatory	↑ cytokines production	↑	=	Kaminska et al. (2016)
	TREM2 myeloid cells receptor	Phagocytosis	↑ phagocytic activity	↑	↑	Wolfe et al. (2019)
	LCN2	Pro-inflammatory	↑ cytokines production and NO	↑	↑	Zamanian et al. (2012) and Bi et al. (2013)
	CCL2, CCL 21, CXCL10 via NF-kB signaling	Pro-inflammatory	↑	↑ recruitment of infiltrating immune cells in CNS	↑	Brambilla et al. (2005), Brambilla et al. (2009), Kim et al. (2014), and Mills Ko et al. (2014)

Principal intracellular pathways involved in the regulation of microglial activity, according to the protective and detrimental roles of microglia. This table highlights the main function of microglia, followed by the specific effect on cellular activation and the effect on the inflammatory and neurodegenerative condition. ↑ and ↓ represent upregulation and downregulation, respectively, = means that the pathway does not affect that condition.