Table 1.
Neuroprotective effects of nAChR-related agents.
| Description | Agent | Action | Model | Ref. |
|---|---|---|---|---|
| Non-selective nAChR agonist | ACh | Activates PI3K/Akt, Nfr2/keap1 | Primary cultured mouse hippocampal neurons treated with Aβ25-35 | [40] |
| Activates Erk1/2 | AD model mice (3xTgAD) | [41] | ||
| Inhibits MAPKs (p38 MAPK, JNK) | Mice intrahippocampally-injected with Aβ1–42 | [42] | ||
| Inhibits phosphorylation of p44/42 and p38 MAPKs → Suppresses TNF-α |
Primary cultured mouse microglia treated with LPS | [23] | ||
| Suppress iNOS, TNF-α, IL-1β → Restores IGF |
Primary cultured mouse microglia treated with LPS | [43] | ||
| Selective α7 nAChR agonist | AR-R17779 | Reverses the pro-inflammatory phenotype | Primary cultured fetal sheep astrocytes | [44] |
| PNU-282987 | Inhibits Erk → Restores 5-HT1A, 2C → Improves anxiety and depressive-like behaviors |
Aβ-injected mice | [45] | |
| Activates CaM-CaMKII-CREB → Improves learning and memory |
AD model mice (APPswe/PSldE9) | [46] | ||
| Selective α7 nAChR partial agonist | A582941 | Increases Erk1/2, MAPKs, Arc → Behavior: pro-cognitive activity |
Rats | [47] |
| DMXBA (GST-21) |
Promotes microglial Aβ phagocytosis → Improves brain Aβ burden and memory Dysfunction → Suppresses γ-secretase activity |
Primary cultured rat microglia Human neuroblastoma SH-SY5Y cells AD model mice (APdE9) |
[48] | |
| Inhibits NF-κB → Suppresses IL-6 and TNF-α Activates Nfr2 → Increases HO-1, TXNRD1, NQO1 |
Primary cultured mouse astrocytes treated with LPS | [49] | ||
| Selective α7 nAChR antagonist | α-bungarotoxin | Enhances the inflammatory phenotype | Primary cultured fetal sheep astrocytes | [44] |
| Type I PAM for α7 nAChR | CCMI | Increases Erk1/2, MAPKs, Arc → Behavior: pro-cognitive activity |
Rats | [47] |
| JWX-A0108 | Inhibits NF-κB → Suppresses TNF-α, IL-1β, IL-6 |
AD model mice (APP/PS1) | [50] | |
| Type II PAM for α7 nAChR | PNU-120596 | Increases: BDNF → Behavior pro-cognitive activity |
Rats | [47] |
| Ago-PAM for α7 nAChR | GAT107 | Suppresses peripheral immune reactions, neuroinflammation | EAE mice | [51] |
| AChE inhibitor | Galantamine | Activates JNK → Increases α7 nAChRs Inhibits Akt → Induces autophagy → Promotes Aβ sequestration |
Human neuroblastoma SH-SY5Y cells | [52] |
| Enhances nAChR sensitivity to choline → Activates CaM-CaMKII and CaM- Rac1-WAVE signaling → Promotes microglial Aβ phagocytosis |
Primary cultured rat microglia AD model mice (APdE9) |
[53] | ||
| Simultaneous stimulation Selective α7 nAChR agonist Selective σ1 receptor agonist |
PHA-543613 PRE-084 |
Modulates glial cells → Increases ACh by σ1-R stimulation |
6-OHDA rat model of PD | [54,55] |
| Simultaneous stimulation Selective α7 nAChR agonist Selective α4β2 nAChR agonist |
PNU-282987 RJR-2403 oxalate |
Inhibits dephosphorylation of AMPAR GluA1 subunit → Reduces AMPARs |
Primary cultured mouse hippocampal neurons treated with Aβ1–42 oligomers | [56] |
| NAD-dependent deacetylase | SIRT1 | Activates Erk1/2 → Increases α7 nAChRs |
AD model mice (APdE9) Human neuroblastoma SH-SY5Y cells |
[57] |
5-HT, hydroxytryptamine; Aβ, amyloid β; ACh, acetylcholine; AChE, acetylcholinesterase; AD, Alzheimer’s disease; AMPAR, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor; Arc, activity-regulated cytoskeleton associated protein; BDNF, brain-derived neurotrophic factor; CaMKII, Ca2+/calmodulin-dependent protein kinase II; CaM, calmodulin; cAMP, cyclic adenosine monophosphate; CREB, cAMP response element binding protein; DMXBA, 3-[(2,4-dimethoxy)benzylidene]-anabaseine dihydrochloride; EAE, experimental autoimmune encephalomyelitis; Erk, extracellular signal-regulated kinase; HO-1, heme oxygenase 1; IGF, insulin-like growth factor; IL, interleukin; iNOS, inducible nitric oxide synthase; JNK, c-Jun N-terminal kinase; keap1, kelch-like ECH-associated protein 1, LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinase; nAChR, nicotinic acetylcholine receptor; NAD, nicotinamide adenine dinucleotide; NF-κB, nuclear factor-κB; Nfr2, nuclear factor erythroid 2-related factor 2; NQO1, NAD(P)H:quinone oxidoreductase 1; PAM, positive allosteric modulator; PD, Parkinson’s disease; PI3K, phosphoinositide 3-kinase; Rac1, Ras-related C3 botulinum toxin substrate 1; SIRT1, sirtuin 1; TNF-α, tumor necrosis factor-α; TXNRD1, thioredoxin reductase 1; WAVE, Wiskott–Aldrich syndrome protein family verprolin-homologous protein.