Table 1.

The origins, receptors and potential biological effects of alarmins in neuroinflammation

Alarmin	Origin	Receptor	Potential Biological Effects	Ref.
HMGB1	Tissue damage	TLR4, RAGE	ROS-mediated JNK activation; NADPH-dependent ROS generation; oxidative stress signaling; autophagy; apoptosis; metabolic impairment	[119,120,121,122,123,124,125]
BAG3	Stressful stimuli	Hsc70/Hsp70 ATPase domain	Chaperone-assisted selective autophagy; hsp70-dependent and independent functions; maintaining the intracellular levels of anti-apoptotic factors and other molecules; protein quality control; cytoskeleton dynamics; structural and functional roles in myocytes	[139,140,141]
S100	Damaged cells	RAGE	ROS-mediated JNK activation; NADPH-dependent ROS generation	[125]
β-amyloid	AD pathogenesis	RAGE	ROS-mediated JNK activation; NADPH-dependent ROS generation	[125]
S1P	Activated platelets in the vasculature	Phagocytosis receptors, including MerTK and MFG-E8 on macrophages	Efficient phagocytosis; recruitment and priming of macrophages;	[75,76]
Spz5	Cell damage or necrotic death	Toll-1 receptor	Prepares, or primes, glia for phagocytosis in the CNS; activates M1-relevant ERK1/2 and JNK in post-ischemic brain	[72,77]
Fractalkine	Apoptotic neurons	CX3CR1	Activation of the proinflammatory pathway mediated by NF-κB as an early response in microglial cells	[78,79]
Hsp	Stressful conditions	TLR family	Inhibition of both aminoglycoside- and cisplatin-induced hair cell death in whole-organ cultures of utricles from adult mice	[112,113]
Hsp32	Trauma; hemorrhage; H2S preconditioning		Neuroprotection; mediation of the protective effect of celastrol; inhibition of pro-apoptotic JNK activation and hair cell death	[112]
Hsp70	Necrotic cells; paraquat-induced oxidative stress; caspase-3-mediated dopaminergic neuronal cell death	c-Type lectin receptors (CLR) and scavenger receptors (SR)	Reduction of paraquat-induced oxidative stress, JNK- and caspase-3-mediated dopaminergic neuronal cell death; decrease in the activated forms of JNK and p38 in the hippocampus of a rat model of fear memory consolidation	[107]
HSP/c70	Damaged astrocytes	TLR4	Activation of JNK in macrophage RAW264.7 cells	[106]
Hsp90	Stressful conditions	Glucocorticoid receptor	Neuroprotection	[114]
α-Synuclein	PD pathogenesis		Innate and adaptive immune responses; direct effects on immune cells, including microglia, initiating a sterile response essential for the neuronal health and translating in a peripheral immune response	[189,190]