Table 1.

Signaling mechanism, G-protein-coupled lysophospholipids receptors, and their identified physiological and pathological functions.

Receptors	G proteins	Signaling pathways	Biological functions	Pathological events
LPARs				-Neurodegeneration (Choi and Chun, 2013; Yung et al., 2015).
LPA1	Gi/o	PLC↑, MAPK↑, PI3K/Akt↑, Rac↑ AC↓, cAMP↓	-Neuronal development (Contos et al., 2000; Fukushima et al., 2002a; Kihara et al., 2014; Suckau et al., 2019); -Neurogenesis of adult hippocampus (Fukushima et al., 2002a);	-Neuropathic pain (Choi et al., 2010); -Ischemic stroke (Savitz et al., 2006; Kimura et al., 2008); -Schizophrenia (Cunningham et al., 2006; Musazzi et al., 2011); -Behavioral dysfunctions (Santin et al., 2009); -Seizure (Elmes et al., 2004).
	G12/13	Rho↑	-Survival and differentiation of neural progenitor cells (NPCs; Chun et al., 2002; Fukushima et al., 2002a; Yung et al., 2014);
	Gq/11	PLC↑, (Ca2+)i↑	-Modulation of adult hippocampus neuroplasticity (García-Morales et al., 2015; Peñalver et al., 2017; Roza et al., 2019); -Negative feedback of microglia induced inflammation (Awada et al., 2014; Kwon et al., 2018).
LPA2	Gi/o	PLC↑, MAPK↑, PI3K/Akt↑, AC↓, cAMP↓	-Neuronal development (Suckau et al., 2019); -Neuronal differentiation (Spohr et al., 2008; E Spohr et al., 2011);	-Seizure (Elmes et al., 2004; Trimbuch et al., 2009).
	G12/13	Rho↑	-Survival and differentiation of neural progenitor cells (NPCs; Chun et al., 2002);
	Gq/11	PLC↑, (Ca2+)i↑	-Neuronal hyperexcitability and neuro-plasticity (Broggini et al., 2010; Coiro et al., 2014);
LPA3	Gi/o	PLC↑, MAPK↑, PI3K/Akt↑, AC↓, cAMP↓	-Neurite branching (Furuta et al., 2012; Roza et al., 2019);	-Neuropathic pain (Ma et al., 2009).
	Gq/11	PLC↑, (Ca2+)i↑
LPA4	Gi/o	PLC↑, MAPK↑, PI3K/Akt↑, Rac↑ AC↓	-Morphogenesis and migration of newborn cortical neurons (Kurabayashi et al., 2018);
	G12/13	Rho↑
	Gq/11	PLC↑, (Ca2+)i↑
	Gs	AC↑, cAMP↑
LPA5	G12/13	Rho↑	-Promotion of microglia migratory response and shift to a pro-inflammatory phenotype (Plastira et al., 2016, 2017).	-Neuropathic pain (Lin et al., 2012).
	Gq/11	PLC↑, (Ca2+)i↑
LPA6	G12/13	Rho↑
S1PRs				-Neurodegeneration (Chakrabarti et al., 2016; Karunakaran and van Echten-Deckert, 2017).
S1P1	Gi/o	PLC↑, PI3K/Akt↑, Rac↑, ERK ↑	-Neurogenesis and brain development (Mizugishi et al., 2005) -Neurite extension (Toman et al., 2004); -Inhibition of cortical glutamatergic neurotransmission (Sim-Selley et al., 2009);	-Neuropathic pain (Sheng et al., 2014; Boyette-Davis et al., 2015); -Multiple sclerosis (Choi et al., 2011); -Spinal cord injury (Goldshmit et al., 2010);
S1P2	Gi/o	PLC↑, PI3K/Akt↑, Rac↑, ERK ↑	-Neurite extension (Toman et al., 2004); -Regulation of neuronal excitability (MacLennan et al., 2001).	-Seizure (MacLennan et al., 2001); -Ischemic stroke (Kimura et al., 2008); -Behavioral dysfunctions (Akahoshi et al., 2011);
	G12/13	Rho↑, Rac↓
	Gq/11	PLC↑, (Ca2+)i↑
S1P3	Gi/o	PLC↑, PI3K/Akt↑, Rac↑, ERK ↑
	G12/13	Rho↑, Rac↓
	Gq/11	PLC↑, (Ca2+)i↑
S1P4	Gi/o	PLC↑, PI3K/Akt↑, Rac↑, ERK ↑
	G12/13	Rho↑, Rac↓
S1P5	Gi/o	PLC↑, PI3K/Akt↑, Rac↑, ERK ↑	-Inhibition of oligodendrocyte progenitor cells (OPCs) migration (Novgorodov et al., 2007).	-Multiple sclerosis (Miron et al., 2010).
	G12/13	Rho↑, Rac↓