Temporal Expression of Apelin/Apelin Receptor in Ischemic Stroke and its Therapeutic Potential

Abstract

Stroke is one of the leading causes of death and disability worldwide, and ischemic stroke accounts for approximately 87% of cases. Improving post-stroke recovery is a major challenge in stroke treatment. Accumulated evidence indicates that the apelinergic system, consisting of apelin and apelin receptor (APLNR), is temporally dysregulated in ischemic stroke. Moreover, the apelinergic system plays a pivotal role in post-stroke recovery by inhibiting neuronal apoptosis and facilitating angiogenesis through various molecular pathways. In this review article, we summarize the temporal expression of apelin and APLNR in ischemic stroke and the mechanisms of their dysregulation. In addition, the protective role of the apelinergic system in ischemic stroke and the underlying mechanisms of its protective effects are discussed. Furthermore, critical issues in activating the apelinergic system as a potential therapy will also be discussed. The aim of this review article is to shed light on exploiting the activation of the apelinergic system to treat ischemic stroke.

Regulation of mRNA Translation in Neurons—A Matter of Life and Death

“…Several human diseases, including neurological disorders, have been linked to mutations in tRNA modification enzymes, and this topic has been the subject of recent comprehensive reviews (Bednářová et al, 2017; Torres et al, 2014). Recently, homozygous mutations in KAE1 (kinase-associated endopeptidase; OSGEP ), which plays a role in the biosynthesis of N 6 -threonylcarbamoyladenosine (t 6 A) modifications of tRNA, have been linked progressive cerebellar atrophy and leukodystrophy (Edvardson et al, 2017).…”

Can Apelin play a role in the etiology of tinnitus?

“…Apelin heals ischemic strokes by inhibiting cell death and increasing angiogenesis. Oxidative stress associated with ischemia/reperfusion injury is reduced by increases in the activities of antioxidant enzymes such as superoxide dismutase, catalase, and kidney glutathione peroxidase (16). In an animal study, Chen et al found that intranasal apelin was a useful stroke treatment (17).…”

The Protective Effects and Mechanisms of Apelin/APJ System on Ischemic Stroke: A Promising Therapeutic Target

“…Compared with the normoxia control group, the expression of APJ in the mouse hippocampus is significantly reduced after 4 weeks of chronic normobaric hypoxia treatment, which can be reversed by apelin-13 (39). Oxidative stress, ERS, autophagy, and inflammatory responses and the interaction between them may be related to the downregulated expression of the apelin/APJ system (18,40,41). For example, ERS, which is activated only during the reperfusion phase rather than the ischemic phase, plays critical roles in cerebral I/R injury (42)(43)(44).…”

“…The expression of the apelin/APJ system components in different stages of ischemic stroke is temporally altered (18). A number of transcription factors, including Sp1 transcription factor (SP1), hypoxia inducible factor 1 alpha (HIF-1α), activating transcription factor 4 (ATF4), signal transducer and activator of transcription 3 (STAT3), and so on, are involved in regulating the expression of the apelin/APJ system (30)(31)(32)(33)(34).…”

“…The apelin/APJ system is widely expressed in the central nervous system, especially in neurons and oligodendrocytes (15,16). Growing evidence indicates that the apelin/APJ system is involved in the pathophysiology of ischemic stroke (17,18). Targeting the apelin/APJ system may have protective effects on cerebral ischemic injury.…”