TABLE 4.
Dopaminergic receptors reported to be involved in Alzheimer’s disease.
| GPCRs | Subtype | Agent | Subject | Second messenger | Mode of action | References |
| D1-like receptor | L-stepholidine (A) | Cell and mouse | ↑ PKA | ↑ AMPAR and p-GluA1Ser845, synaptic function, and cognition | Hao et al., 2015 | |
| L-theanine (A) | Mouse | ↑ PKA | ↑ Synaptic function and cognition | Zhu et al., 2018 | ||
| SKF-38393 (A) | Cell and rat | ↑ PKA and CDK5 ↓ GSK-3β | ↑ Tau | Lebel et al., 2009 | ||
| Mouse | ↑ SFK | ↓ oAβ neurotoxicity ↑ Synaptic function and cognition | Yuan Xiang et al., 2016 | |||
| Mouse | ↑ p-CREB | ↓ Aβ, BACE1 and neuronal apoptosis ↑ BDNF and cognition | Zang et al., 2018 | |||
| SKF81297 (A) | Rat | ND | ↑ AMPAR and p-GluA1Ser845, NMDAR and synaptic function | Jurgensen et al., 2011 | ||
| DA1R | A-68930 (A) | Cell and mouse | ↑ AMPK | ↓ Neuroinflammation and neuronal damage ↑ Cognition | Cheng et al., 2020 | |
| Cell and mouse | ↑ AMPK and PGC-1α | ↓ Aβ, BACE1, tau, and mitochondrial dysfunction ↑ Cognition | Cheng et al., 2021 | |||
| DA5R | 027075 (A) | Mouse | ↑ cAMP | ↓ Aβ, BACE1, PS1, and apoptosis ↑ NEP, cell differentiation, neurite length, and cognition | Shen et al., 2016 | |
| D2-like receptor | DA2/3R | Rotigotine (A) | Human | ND | ↑ Cortical excitability and cholinergic transmission | Martorana et al., 2013 |
| DA2R | Levodopa or piribedil (A) | Cell and mouse | ↑β-arrestin2 | ↑ Aβ and γ-secretase | Lu et al., 2017 | |
| Quinpirole (A) | Cell and mouse | ND | ↓ Aβ42 neurotoxicity | Melief et al., 2015 |
A, agonists; A-68930, (1R, 3S)-1-aminomethyl-5,6-dihydroxy-3-phenylisochroman HCI; Aβ, amyloid-β; AMPAR,α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptors; AMPK, adenine monophosphate activated protein kinase; AN, antagonists; BACE1,β-secretase; cAMP, cyclic adenosine monophosphate; CDK5, cyclin-dependent kinase 5; CREB, cAMP-response element binding protein; GSK-3β, glycogen synthase kinase-3β; LTP, long term potentiation; ND, not determined; NEP, neprilysin; NMDA, N-methyl-D-aspartate receptors; oAβ, Aβ oligomer; PGC-1α, peroxisome-proliferator-activated receptorγcoactjvator-1α; PKA, cyclic-AMP dependent protein kinase A; PS1, presenilin 1; SFK, Src-family tyrosine kinases; SKF-38393, (7,8-dihydroxy-1-phenyl-2,3,4,5-tetrahydro-1 H-3-benzazepine); SKF81297, (6-chloro-7,8-dihydroxy-1-phenyl-2,3,4,5- tetrahydro-1 H-3-benzazepine).