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. 2022 May 18;14:869507. doi: 10.3389/fnagi.2022.869507

TABLE 2.

Adrenergic receptors reported to be involved in Alzheimer’s disease.

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.