Table 1.

Pathways Associated with the Modulation of Murine and Human Reactive Astrocytes^a

Functional category	Molecule	Signaling pathway	Effect on reactive astrocytes	Refs
Cytokines	IL-6	GP130–JAK/STAT3	Regulates expression of GFAP, vimentin, STAT3 and other genes with STAT responsive elements	[24]
	CNTF	GP130–JAK/STAT3	Regulates expression of GFAP, vimentin, STAT3, and other genes with STAT responsive elements	[24]
	TGF-β	SMAD	Increases vimentin, actin, and GFAP expression; contributes to scar formation	[115]
	IL-1β	NF-κB	Proinflammatory	[24]
	TNF	NF-κB/CN–NFAT	Activates expression of target genes	[24]
	IFN-α/β	STAT1/STAT2	Antiviral	[37]
	IFN-γ	IFNGR–JAK/STAT1	Potentiates astrocyte reactivity	[116]
DAMPS	ATP	P2XR/P2YR–Ca2+	Proinflammatory	[117]
	ROS	NF-κB, PI3K, MAPK	Proinflammatory	[118]
	NO	Soluble guanylyl cyclase	Proinflammatory (mitochondrial impairment, neuronal injury and death)	[119]
Growth factors	EGF	MAPK	Expression of inducible NO synthase, GFAP, modification of the extracellular matrix, proliferation	[120]
	FGF	MAPK	FGF family members show differentially regulatory roles	[24]
	TGF-α	MAPK	Induces expression of GFAP and vimentin and morphological features of reactive astrocytes	[121]
Hormones	Progesterone	Progesterone receptors	Anti-inflammatory	[122]
	Androgens	Androgen receptors	Anti-inflammatory	[123]
	Estradiol	Estrogen receptors	Anti-inflammatory	[124]
Neurodegeneration	Amyloid beta	RAGE/NF-κB	Proinflammatory (inflammatory cytokines and NO)	[125]
Neurotransmitters	Glutamate	CN–NFAT	Context dependent (triggers or inhibits astrocyte reactivity)	[24]
PAMPs	LPS	TLR4/NF-κB	Proinflammatory	[126]
	dsRNA (poly I:C)	TLR3	Antiviral and proinflammatory	[127]
	ssRNA	TLR7–Myd88/NF-κB	Antiviral and proinflammatory	[128]
	CpG DNA	TLR9–Myd88/NF-κB	Antiviral and proinflammatory	[128]
	Cytosolic DNA	cGAS–STING/IFN	Antiviral and proinflammatory	[129]

^aAbbreviations: cGAS–STING, cGMP-AMP synthase–stimulator of interferon genes; CN–NFAT, calcineurin-nuclear factor of activated T cells; CNTF, ciliary neurotrophic factor; DAMPs, damage-associated molecular patterns; EGF, epidermal growth factor; FGF, fibroblast growth factor; GP130, glycoprotein 130; IFNGR, IFN-γ receptor; Myd88, myeloid differentiation primary response 88; NO, nitric oxide; P2XR, P2X receptor; P2YR, P2Y receptor; PI3K, phosphatidylinositol-3-kinase; RAGE, receptor for advanced glycation end products; ROS, reactive oxygen species; ssRNA, single-stranded RNA.