apelin-13-peptide and Alzheimer-Disease

Alzheimer's disease (AD) is the most common type of dementia. Currently, more than 50 million people live with dementia worldwide, and this number is expected to increase. Some of the typical pathological changes of AD include amyloid plaque, hyperphosphorylation of tau protein, secretion of inflammatory mediators, and neuronal apoptosis. Apelin is a neuroprotective peptide that is widely expressed in the body. Among members of apelin family, apelin-13 is the most abundant with a high neuroprotective function. Apelin-13/angiotensin domain type 1 receptor-associated proteins (APJ) system regulates several physiological and pathophysiological cell activities, such as apoptosis, autophagy, synaptic plasticity, and neuroinflammation. It has also been shown to prevent AD development. This article reviews the research progress on the relationship between apelin-13 and AD to provide new ideas for prevention and treatment of AD.

Topics: Alzheimer Disease; Apelin Receptors; Autophagy; Humans; Intercellular Signaling Peptides and Proteins; tau Proteins

Alzheimer's disease (AD) by progressive neurodegenerative pattern is associated with autophagy stress which is suggested as a potential cause of amyloid β (Aβ) aggregation and neural loss. Apelin-13, a neuropeptide with modulatory effect on autophagy, has been shown the beneficial effects on neural cell injuries. We investigated the effect of Apelin-13 on Aβ-induced memory deficit as well as autophagy and apoptosis processes. We performed bilateral intra-CA1 injection of Aβ25-35 alone or in combination with Apelin-13. Spatial reference and working memory was evaluated using the Morris water maze (MWM) and Y-maze tests. Hippocampus was harvested on 2, 5, 10 and 21 days after Aβ injection. The light chain 3 (LC3II/I) ratio, histone deacetylase 6 (HDAC6) level, Caspase-3 cleavage, and mTOR phosphorylation were assessed using western blot technique. Intra-CA1 injection of Aβ caused impairment of working and spatial memory. We observed higher LC3II/I ratio, cleaved caspase-3 and lower HDAC6, and p-mTOR/mTOR ratio in Aβ-treated animals. Apelin-13 provided significant protection against the destructive effects of Aβ on working and spatial memory. Apelin-13 prevented the increase of LC3II/I ratio and cleaved caspase-3 on days 10 and 21 after injection of Aβ. It also limited the Aβ-induced reduction in HDAC6 expression. This implies that Apelin-13 has suppressed both autophagy and apoptosis. Our findings suggested that the neuroprotection of Apelin-13 may be in part related to autophagy and apoptosis inhibition via the mTOR signaling pathway. Apelin-13 may be a promising approach to improve memory impairment and potentially pave the way for new therapeutic plans in AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Apoptosis; Autophagy; Dose-Response Relationship, Drug; Hippocampus; Histone Deacetylase 6; Intercellular Signaling Peptides and Proteins; Male; Memory; Memory Disorders; Motor Activity; Neuroprotective Agents; Peptide Fragments; Random Allocation; Rats, Wistar; TOR Serine-Threonine Kinases

Apelin-13 is known to be one of the predominant neuropeptides with marked protective role in circuits involved in mood disturbances. The most putative hypothesis in pathophysiology of Alzheimer's disease (AD) is Amyloid beta (Aβ) aggregation which interrupt proper function of hypothalamic-pituitary-adrenal (HPA) axis and are associated with anxiety. Here, we assessed the potential anxiolytic effect of Apelin-13 in a rodent cognitive impairment model induced by intrahippocampal Aβ 25-35 administration. We evaluated the memory impairment and anxiogenic behavior using shuttle box and Elevated plus maze apparatuses. We also measured the glucocorticoid receptor (GR) and FK506 binding protein 51 (FKBP5) expression as important markers showing the proper feedback mechanism within the HPA axis. Our findings showed that Aβ 25-35 administration induced memory impairment and anxiety behaviors. Apelin-13 exerted the anxiolytic effects and provided protection against Aβ 25-35 -induced passive avoidance memory impairment. Moreover, Apelin-13 caused an increase in GR and a decrease in FKBP5 expression levels in Aβ 25-35 treated animals. Taken together, these findings showed the anxiolytic effect of Apelin-13. This effect at least in part, may be mediated through the regulation of GR and FKBP5 expression levels which have a pivotal role in the appropriate negative feedback mechanism within the HPA axis. These data suggest that Apelin-13 might be considered as a potential neuropeptide defense that reduces anxiety along with neuroprotective effect against the Aβ 25-35 -induced injury.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Animals; Anxiety; Blotting, Western; CA1 Region, Hippocampal; Hypothalamo-Hypophyseal System; Intercellular Signaling Peptides and Proteins; Male; Memory Disorders; Peptide Fragments; Pituitary-Adrenal System; Random Allocation; Rats; Rats, Wistar; Receptors, Glucocorticoid; Tacrolimus Binding Proteins