TABLE 2.
GPCRs | Subtype | Agent | Subject | Second messenger | Mode of action | References |
α1-AR | Doxazosin (AN) | Cell | ↑ EGFR and Akt ↓ GSK-3β | ↓ Aβ neurotoxicity and tau | Coelho et al., 2019 | |
Prazosin (AN) | Cell and mouse | ND | ↓ Aβ40 and neuroinflammation ↑ sAPPα, neuronal number and cognition | Katsouri et al., 2013 | ||
α2-AR | Dexefaroxan (AN) | Mouse | ND | ↑ BDNF and cognition →Aβ | Francis et al., 2012 | |
Fluparoxan (AN) | Mouse | ND | ↑ Cognition →Amyloid plaque and neuroinflammation | Scullion et al., 2011 | ||
Mesedin (AN) | Mouse | ND | ↓ Aβ and neuroinflammation ↑ neurogenesis, neuronal maturation, neuronal and astroglial protection | Melkonyan et al., 2017 | ||
α2A-AR | BRL-44408 (AN) | Mouse | ND | ↓ Aβ↑ Cognition | Chen et al., 2014 | |
β-AR | Carvedilol (AN) | Rat | ND | ↓ Oxidative damage ↑ Cognition | Kumar et al., 2011 | |
Mouse | ND | ↓ oAβ↑ Cognition | Wang J. et al., 2011 | |||
Cell | ND | ↓ Aβ neurotoxicity, oxidative stress and apoptosis | Liu and Wang, 2018 | |||
Isoproterenol (A) | Rat | ↑ PKA | ↑ Tau and oxidative stress | Wang et al., 2004 | ||
Rat | ↑ PKA, CaMKII and CDK5 ↓ PP2A | ↑ Tau ↓ Cognition | Sun et al., 2005 | |||
Cell and mouse | ND | ↑γ-secretase, PS1 and Aβ | Ni et al., 2006 | |||
Cell | ↑ ERK1/2 and p38 ↓ NF-κB | ↓ Aβ42 ↑ IDE | Kong et al., 2010 | |||
Cell and mouse | ND | ↓ Tau | Soeda et al., 2015 | |||
Mouse | ND | ↓ Microglial inflammation | Xu et al., 2018 | |||
Propranolol (AN) | Mouse | ↑ Akt ↓ JNK and GSK-3β | ↓ Aβ and tau ↑ IDE and cognition | Dobarro et al., 2013a | ||
↑ Akt and GSK-3β | ↓ Aβ42, BACE1, and tau ↑ IDE, BDNF, SYP, and cognition | Dobarro et al., 2013b | ||||
β1-AR | Xamoterol (A) | Mouse | ↑ PKA and CREB | ↑ Cognition | Coutellier et al., 2014 | |
Cell and mouse | ↑ cAMP | ↓ Aβ, tau, and neuroinflammation | Ardestani et al., 2017 | |||
β2-AR | Clenbuterol (A) | Mouse | ND | ↑ Aβ | Yu et al., 2010 | |
Mouse | ND | ↓ Aβ and p-APPThr668 ↑ Synaptic plasticity, neurogenesis, and cognition | Chai et al., 2016 | |||
Cell and mouse | ND | ↓ Aβ and p-APPThr668 ↑α-secretase, synaptic plasticity and cognition | Chai et al., 2017 | |||
Formoterol (A) | Mouse | ↓ GSK-3β | ↓ Oxidative stress, apoptosis and neuroinflammation ↑ Cognition | Abdel Rasheed et al., 2018 | ||
ICI-118551 (AN) | Mouse | ND | ↓ Aβ | Ni et al., 2006 | ||
Mouse | ND | ↓ Aβ | Yu et al., 2010 | |||
Mouse | ND | ↑ Aβ, Amyloid plaques and tau ↓ Cognition | Branca et al., 2014 | |||
Mouse | ND | ↑ Aβ and p-APP ↓α-secretase, synaptic plasticity and cognition | Wu et al., 2017 | |||
Terbutaline (A) | Rat | ↑ cAMP and PKA | ↑ LTP | Wang et al., 2009 | ||
β3-AR | CL-316243 (A) | Chick | ND | ↑ Cognition | Gibbs et al., 2010 | |
Mouse | ND | ↓ Insoluble Aβ42/Aβ40 ratio ↑ Cognition | Tournissac et al., 2021 |
A, agonist; Aβ, amyloid-β; AN, antagonist; APP,β-amyloid precursor protein; Akt, protein kinase B; AR, adrenergic receptor; BACE1,β-secretase; BDNF, brain-derived neurotrophic factor; BRL-44408, (2-[2H-(1-methyl-1,3-dihydroisoindole) methyl]-4,5-dihydroimidazole); cAMP, cyclic adenosine monophosphate; CaMKII, Calcium/calmodulin-dependent protein kinase II; CDK5, cyclin-dependent kinase 5; CL-316243, 5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]-amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate; CREB, cAMP-response element binding protein; EGFR, epidermal growth factor receptor; ERK, extracellular regulated protein kinases; GSK-3β, glycogen synthase kinase-3β; ICI-118551, 3-(isopropylamino)-1-((7-methyl-2,3-dihydro-1H-inden-4-yl)oxy)butan-2-ol hydrochloride; IDE, insulin degrading enzyme; JNK, C-Jun kinase enzyme; LTP, long term potentiation; ND, not determined; NF-κB, nuclear factor kappa-B; oAβ, Aβ oligomer; p38, p38 mitogen-activated protein kinases; PKA, cyclic-AMP dependent protein kinase A; PP2A, protein phosphatase-2A; PS1, presenilin 1; SYP, synaptophysin.