Abstract:Apelin is a bioactive peptide and an endogenous ligand for the angiotensin Ⅱ type one receptor-related protein APJ. Its precursor can be cleaved into various active fragments by proteases, with Apelin-13 having the strongest affinity with APJ. Apelin-13 is widely present in the central nervous system and exerts neuroprotective effects by regulating cell apoptosis, autophagy, synaptic plasticity, neuroinflammation, and oxidative stress. Neurons play an important role in the development and maturation of the nervous system, and neuronal damage is closely related to cognitive dysfunction. Therefore, the neuroprotective effect mediated by Apelin-13 has great potential for improving cognitive impairment caused by various reasons. This article reviews the latest research progress of Apelin-13 in cognitive impairment, which is expected to provide new targets and strategies for the treatment of cognitive impairment.
师利敏 刘海军 徐平▲. Apelin-13在认知功能障碍中相关机制的研究进展[J]. 中国医药导报, 2023, 20(31): 48-51.
SHI Limin LIU Haijun XU Ping▲. Research progress on the related mechanisms of Apelin-13 in cognitive dysfunction. 中国医药导报, 2023, 20(31): 48-51.
[1] World Health Organization. Global status report on the public health response to dementia:executive summary [EB/OL].[2021-09-01]. https://www.who.int/publications/i/item/978924 0033245. [2] World Health Organization. Global action plan to address dementia in the public health sector [EB/OL].[2017-05-31].https://www.who.int/publications/i/item/9789241513487. [3] Tatemoto K,Hosoya M,Habata Y,et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor [J]. BiochemBiophys Res Commun,1998, 251(2):471-476. [4] Kawamata Y,Habata Y,Fukusumi S,et al. Molecular properties of apelin:tissue distribution and receptor binding [J]. BiochimBiophys Acta,2001,1538(2-3):162-171. [5] O’Carroll AM,Selby TL,Palkovits M,et al. Distribution of mRNA encoding B78/APJ,the rat homologue of the human APJ receptor,and its endogenous ligand apelin in brain and peripheral tissues [J]. BiochimBiophys Acta,2000,1492(1): 72-80. [6] Luo H,Xiang Y,Qu X,et al. Apelin-13 suppresses neuroinflammation against cognitive deficit in a streptozotocin-induced rat model of Alzheimer’s disease through activation of BDNF-TrkB signaling pathway [J]. Front Pharmacol,2019, 10:395. [7] Hu S,Shen P,Chen B,et al. Apelin-13 reduces lipopolysaccharide-induced neuroinflammation and cognitive impairment via promoting glucocorticoid receptor expression and nuclear translocation [J]. Neurosci Lett,2022,788:136850. [8] Elmore S. Apoptosis:a review of programmed cell death [J]. Toxicol Pathol,2007,35(4):495-516. [9] Ge X,Zuo Y,Xie J,et al. A new mechanism of POCD caused by sevoflurane in mice:cognitive impairment induced by cross- dysfunction of iron and glucose metabolism [J]. Aging(Albany NY),2021,13(18):22375-22389. [10] Peng Y,Chi R,Liu G,et al. Aerobic exercise regulates apoptosis through the PI3K/Akt/GSK-3β signaling pathway to im- prove cognitive impairment in Alzheimer’s disease mice [J]. Neural Plast,2022,2022:1500710. [11] Glab JA,Cao Z,Puthalakath H,et al. Bcl-2 family proteins,beyond the veil [J]. Int Rev Cell Mol Biol,2020,351:1-22. [12] Lei Q,Huang X,Zheng L,et al. Biosensors for Caspase-3:from chemical methodologies to biomedical applications [J]. Talanta,2022,240:123198. [13] Yan W,Pang M,Yu Y,et al. The neuroprotection of liraglutide on diabetic cognitive deficits is associated with improved hippocampal synapses and inhibited neuronal apoptosis [J]. Life Sci,2019,231:116566. [14] Shao ZQ,Dou SS,Zhu JG,et al. Apelin-13 inhibits apoptosis and excessive autophagy in cerebral ischemia/reperfusion injury [J]. Neural Regen Res,2021,16(6):1044-1051. [15] Yang Y,Zhang X,Cui H,et al. Apelin-13 protects the brain against ischemia/reperfusion injury through activating PI3K/ Akt and ERK1/2 signaling pathways [J]. Neurosci Lett,2014, 568:44-49. [16] Li W,He P,Huang Y,et al. Selective autophagy of intracellular organelles:recent research advances [J]. Theranostics,2021,11(1):222-256. [17] Yang N,Liu X,Niu X,et al. Activation of autophagy ameliorates age-related neurogenesis decline and neurodysfunction in adult mice [J]. Stem Cell Rev Rep,2022,18(2):626- 641. [18] Gao S,Tang YY,Jiang L,et al. H2S attenuates sleep deprivation-induced cognitive impairment by reducing excessive autophagy via hippocampal sirt-1 in WISTAR RATS [J].Neurochem Res,2021,46(8):1941-1952. [19] Zhu J,Dou S,Jiang Y,et al. Apelin-13 protects dopaminergic neurons in MPTP-induced Parkinson’s disease model mice through inhibiting endoplasmic reticulum stress and promoting autophagy [J]. Brain Res,2019,1715:203-212. [20] Ge Y,Zhou M,Chen C,et al. Role of AMPK mediated pathways in autophagy and aging [J]. Biochimie,2022,195:100- 113. [21] Li S,Zhou Y,Hu H,et al. SIRT3 enhances the protective role of propofol in postoperative cognitive dysfunction via activating autophagy mediated by AMPK/mTOR pathway [J]. Front Biosci(Landmark Ed),2022,27(11):303. [22] Kong X,Lin D,Lu L,et al. Apelin-13-mediated AMPK ameliorates endothelial barrier dysfunction in acute lung injury mice via improvement of mitochondrial function and autophagy [J]. Int Immunopharmacol,2021,101(Pt B):108230. [23] Runwal G,Stamatakou E,Siddiqi FH,et al. LC3-positive structures are prominent in autophagy-deficient cells [J]. Sci Rep,2019,9(1):10147. [24] Aminyavari S,Zahmatkesh M,Farahmandfar M,et al. Protective role of Apelin-13 on amyloid β25-35-induced memory deficit,involvement of autophagy and apoptosis process [J]. Prog Neuropsychopharmacol Biol Psychiatry,2019,89:322-334. [25] Li Y,Wang H,Gao Y,et al. Circ-Vps41 positively modulates Syp and its overexpression improves memory ability in aging mice[J]. Front Mol Neurosci,2022,15:1037912. [26] Mardones MD,Jorquera PV,Herrera-Soto A,et al. PSD95 regulates morphological development of adult-born granule neurons in the mouse hippocampus [J]. Chem Neuroanat,2019,98:117-123. [27] Esmaeili-Mahani S,Haghparast E,Nezhadi A,et al. Apelin- 13 prevents hippocampal synaptic plasticity impairment in Parkinsonism rats [J]. Chem Neuroanat,2021,111:101884. [28] Petkova-Tuffy A,G?觟decke N,Viotti J,et al. Neuroligin-1 mediates presynaptic maturation through brain-derived neurotrophic factor signaling [J]. BMC Biol,2021,19(1):215. [29] Gazmeh S,Azhir M,Elyasi L,et al. Apelin-13 protects against memory impairment and neuronal loss,induced by scopolamine in male rats [J]. Metab Brain Dis,2022,37(3):701-709. [30] Jackson L,Dumanli S,Johnson MH,et al. Microglia knockdown reduces inflammation and preserves cognition in diabetic animals after experimental stroke [J].Neuroinflammation,2020,17(1):137. [31] Zborowski VA,Heck SO,Sari MHM,et al. (p-ClPhSe)2 modulates hippocampal BDNF/TrkB signaling and reverses memory impairment induced by diabetes in mice [J]. Prog Neuropsychopharmacol Biol Psychiatry,2019,94:109660. [32] Abbah J,Vacher CM,Goldstein EZ,et al. Oxidative stress-induced damage to the developing hippocampus is mediated by GSK3β [J]. Neurosci,2022,42(24):4812-4827. [33] Lin J,Niu Z,Xue Y,et al. Chronic vitamin D3 supplementation alleviates cognition impairment via inhibition of oxidative stress regulated by PI3K/AKT/Nrf2 in APP/PS1 transgenic mice [J]. Neurosci Lett,2022,783:136725. [34] Duan J,Cui J,Yang Z,et al. Neuroprotective effect of Apelin 13 on ischemic stroke by activating AMPK/GSK-3β/Nrf2 signaling [J]. Neuroinflammation,2019,16(1):24. [35] Mohseni F,Garmabi B,Khaksari M,et al. Apelin-13 attenuates spatial memory impairment by anti-oxidative,anti- apoptosis,and anti-inflammatory mechanism against ethanol neurotoxicity in the neonatal rat hippocampus [J]. Neuropeptides,2021,87:102130. [36] Yildiz Z,Eren N,Orcun A,et al. Serum apelin-13 levels and total oxidant/antioxidant status of patients with Alzheimer’s disease [J]. Aging Med(Milton),2021,4(3):201-205. [37] Acikel SB,Artik A,Hosoglu E,et al. Serum Apelin-13 levels are decreased among adolescents diagnosed with major depressive disorder [J]. Psychiatr Danub,2022,34(4):677- 681.