Table 1.
Apelin/APJ system attenuates neurodegenerative diseases
| Species | Models | Apelin treatments | Mechanisms | Pathways | Refs. |
|---|---|---|---|---|---|
| Rat | STZ-induced dementia | Apelin i.c.v |
Ameliorating neuroinfammation |
TNF-α | [54] |
| Rat | STZ-induced AD |
Apelin-13 2 µg i.c.v |
Anti-inflammatory and anti-tau phosphorylation | BDNF/TrkB | [55] |
| Aβ 25–35 induced AD |
Apelin-13 1, 2, 2.5, 5 μg intra-CA1 injection |
suppressing autophagy and apoptosis | mTOR | [59, 60] | |
| Rat | Aβ 25–35 induced memory impairment and anxiety behaviors |
Apelin-13 2 μg intra-CA1 injection |
Improving avoidance memory deficit and HPA axis feedback mechanism as well as anxiogenic behaviors | FKBP5/GR | [57, 60] |
| Mice | MPTP-induced PD |
Apelin-13 0.3 μg/day SNpc injection |
Alleviating α-synuclein aggregation | IREα/XBP-1/CHOP | [63] |
| Mice | MPTP-induced PD |
Apelin-36 0.1, 0.3, 0.5 μg /day SNpc injection |
Decreasing the aggregation of nitrated α-synuclein and alleviating oxidative stress | ASK1/JNK/caspase-3 SOD/GSH/MDA | [64] |
| Mice | MPTP/MPP + induced PD |
Apelin-36 0.5 μg/day SNpc injection |
Induction of α-synuclein expression | GRP78/CHOP/ cleaved caspase-12 | [65] |
| Rat | Rotenone-treated |
apelin-13 2, 5 µg/kg i.c.v |
Attenuating neurotoxicity | AMPK/mTOR/ULK-1 | [66] |
| Rat | 6-hydroxydopamine infused right substantia nigra |
apelin-13 2,3 µg SNpc injection |
Ameliorating E-LTP impairment | PSD-95, DR1, mGluR1 | [67, 69] |
AD Alzheimer's disease, IL-1β interleukin-1β, TNF-α tumor necrosis factor-α, BDNF brain-derived neurotrophic factor, TrkB tyrosine receptor kinase B, GC glucocorticoid receptor, FKBP5 FK506 binding protein 5, PI3K phosphatidylinositol-3-kinase, Akt protein kinase B, mTOR mammalian target of rapamycin, IRE1 inositol-requiring enzyme 1, XBP1 X-box binding protein 1, CHOP C/EBP homologous protein, ASK1 signal-regulated kinase 1, JNK c-Jun N-terminal kinase, PSD-95 postsynaptic density protein 95, mGluR1 metabotropic glutamate receptor 1, MPP + 1-methyl-4-phenylpyridinium, MPTP 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridin, SNpc substantia nigra compacta, SOD superoxide Dismutase, GSH glutathione, MDA malondialdehyde, GRP78 glucose-regulated protein 78, AMPK AMP-activated kinase, mTOR mammalian target of rapamycin, ULK1 unc-51-like kinase 1, E-LTP early-long-term potentiation