neuropeptide hormone
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2022 ◽  
Vol 1 ◽  
Author(s):  
Christopher R. Apostol ◽  
Kelsey Bernard ◽  
Parthasaradhireddy Tanguturi ◽  
Gabriella Molnar ◽  
Mitchell J. Bartlett ◽  
...  

There is an unmet clinical need for curative therapies to treat neurodegenerative disorders. Most mainstay treatments currently on the market only alleviate specific symptoms and do not reverse disease progression. The Pituitary adenylate cyclase-activating polypeptide (PACAP), an endogenous neuropeptide hormone, has been extensively studied as a potential regenerative therapeutic. PACAP is widely distributed in the central nervous system (CNS) and exerts its neuroprotective and neurotrophic effects via the related Class B GPCRs PAC1, VPAC1, and VPAC2, at which the hormone shows roughly equal activity. Vasoactive intestinal peptide (VIP) also activates these receptors, and this close analogue of PACAP has also shown to promote neuronal survival in various animal models of acute and progressive neurodegenerative diseases. However, PACAP’s poor pharmacokinetic profile (non-linear PK/PD), and more importantly its limited blood-brain barrier (BBB) permeability has hampered development of this peptide as a therapeutic. We have demonstrated that glycosylation of PACAP and related peptides promotes penetration of the BBB and improves PK properties while retaining efficacy and potency in the low nanomolar range at its target receptors. Furthermore, judicious structure-activity relationship (SAR) studies revealed key motifs that can be modulated to afford compounds with diverse selectivity profiles. Most importantly, we have demonstrated that select PACAP glycopeptide analogues (2LS80Mel and 2LS98Lac) exert potent neuroprotective effects and anti-inflammatory activity in animal models of traumatic brain injury and in a mild-toxin lesion model of Parkinson’s disease, highlighting glycosylation as a viable strategy for converting endogenous peptides into robust and efficacious drug candidates.


2021 ◽  
Vol 12 ◽  
Author(s):  
Junko Yamada ◽  
Yo Nakawake ◽  
Qiulu Shou ◽  
Kuniyuki Nishina ◽  
Masahiro Matsunaga ◽  
...  

Spirituality and religiosity have a significant impact on one's well-being. Although previous studies have indicated that the neuropeptide hormone oxytocin is associated with spirituality/religiosity, existing findings remain inconsistent. Some studies have reported a positive relationship between oxytocin and spirituality/religiosity, while other studies have reported a negative association. Herein, we examined the association between endogenous oxytocin and spirituality/religiosity in 200 non-Abrahamic Japanese individuals (102 females, mean age ± standard deviation = 41.53 ± 10.46) by measuring the level of salivary oxytocin and spiritual/religious faith. We found that the level of salivary oxytocin was negatively associated with spiritual/religious faith. Individuals with higher levels of salivary oxytocin tend to have more negative spiritual/religious faith compared with those with low oxytocin levels (e.g., “Spirituality/religiosity makes people passive and clinging.”). Moreover, this tendency was only significant in individuals who were not interested in a specific religion. The uniqueness of spirituality/religiosity in Japan could help interpret the current findings.


2021 ◽  
Vol 19 ◽  
Author(s):  
Liu-Nan Yang ◽  
Kai Chen ◽  
Xiao-Ping Yin ◽  
Dan Liu ◽  
Ling-Qiang Zhu

: Oxytocin (OXT) is a nine amino acid neuropeptide hormone that has become one of the most intensively studied molecules in the past few decades. The vast majority of OXT is synthesized in the periventricular nucleus and supraoptic nucleus of the hypothalamus, and a few are synthesized in some peripheral organs (such as the uterus, ovaries, adrenal glands, thymus, pancreas, etc.) OXT modulates a series of physiological processes, including lactation, parturition, as well as some social behaviors. In addition, more and more attention has recently been focused on the analgesic effects of oxytocin. It has been reported that OXT can relieve tension and pain without other adverse effects. However, the critical role and detailed mechanism of OXT in analgesia remain unclear. Here, this review aims to summarize the mechanism of OXT in analgesia and some ideas about the mechanism.


2020 ◽  
Vol 132 (1) ◽  
pp. 211-220
Author(s):  
Susanna K Campbell ◽  
Liliana Cortés-Ortiz

Abstract Oxytocin is a mammalian neuropeptide hormone that mediates behaviours important to reproduction. Despite almost universal amino acid sequence conservation across most groups of mammals, several unique forms have been reported across Neotropical primates. To explore sequence diversity, we investigated the genes encoding oxytocin and its receptor across the Atelidae, which was known to contain at least three unique oxytocin sequences. Additionally, we included the genus Cebus, within the Cebidae, to further explore the ubiquity of the Pro8 variant in this family. We found a novel amino acid variant (Val3) within the Atelidae radiation, bringing the total number of oxytocin sequences within Neotropical primates to seven. Analyses of physicochemical properties revealed conservative substitutions that are likely tolerated within the selective constraints imposed by receptor binding. Furthermore, we report radical substitutions at the eighth codon and evidence for co-evolution between Pro8 and a ligand-binding region of the oxytocin receptor in the Atelidae, supporting the notion that this variant may affect binding specificity. Overall, we suggest that selective constraint on binding specificity may maintain proper oxytocin function and that the diversification of amino acid sequence is likely due to a variety of processes such as relaxed constraint, neutral mutation, positive selection and coevolution.


2020 ◽  
pp. 107385842096011
Author(s):  
Nina Marsh ◽  
Abigail A. Marsh ◽  
Mary R. Lee ◽  
René Hurlemann

Humans are an unusually prosocial species, who engage in social behaviors that include altruism—whereby an individual engages in costly or risky acts to improve the welfare of another person—care, and cooperation. Current perspectives on the neurobiology of human prosociality suggest that it is deeply rooted in the neuroendocrine architecture of the social brain and emphasize the modulatory role of the neuropeptide hormone oxytocin. In this review, we provide a conceptual overview of the neurobiology of prosocial behavior with a focus on oxytocin’s modulatory role in human prosociality. Specifically, we aim to encourage a better understanding of the peptide’s susceptibility to diverse factors that produce heterogeneity in outcomes and the resulting methodological implications for measuring the behavioral effects of oxytocin in humans. After providing an overview of the state-of-the-art research on oxytocin’s exogenous use, we elaborate on the peptide’s modulatory role in the context of care-based altruism, cooperation, and conflict and discuss its potential for therapeutic interventions in psychiatric disorders characterized by social dysfunction.


2020 ◽  
Vol 36 (10) ◽  
pp. 849-853
Author(s):  
Giray Bozkaya ◽  
Ozge Fenercioglu ◽  
İsmail Demir ◽  
Aslı Guler ◽  
Behnaz Aslanipour ◽  
...  

2019 ◽  
Author(s):  
Kazuhiro Kobayashi ◽  
Wataru Shihoya ◽  
Tomohiro Nishizawa ◽  
Francois Marie Ngako Kadji ◽  
Junken Aoki ◽  
...  

AbstractPituitary adenylate cyclase-activating polypeptide (PACAP) is a pleiotropic neuropeptide hormone functioning in the central nervous system and peripheral tissues. The PACAP receptor PAC1R, which belongs to the class B G-protein-coupled receptors (GPCRs), is a drug target for mental disorders and dry eye syndrome. Here we present a cryo-electron microscopy structure of human PAC1R bound to PACAP and an engineered Gs heterotrimer. The structure revealed that TM1 plays an essential role in PACAP recognition. The ECD (extracellular domain) of PAC1R tilts by ~40° as compared to that of the glucagon-like peptide-1 receptor (GLP1R), and thus does not cover the peptide ligand. A functional analysis demonstrated that the PAC1R-ECD functions as an affinity trap and is not required for receptor activation, whereas the GLP1R-ECD plays an indispensable role in receptor activation, illuminating the functional diversity of the ECDs in the class B GPCRs. Our structural information will facilitate the design and improvement of better PAC1R agonists for clinical applications.This article is a preprint version and has not been certified by peer review.


2019 ◽  
Author(s):  
Gonzalo Quiroga Artigas ◽  
Pascal Lapébie ◽  
Lucas Leclère ◽  
Philip Bauknecht ◽  
Julie Uveira ◽  
...  

AbstractThe reproductive hormones that trigger oocyte meiotic maturation and release from the ovary vary greatly between animal species. Identification of receptors for these Maturation Inducing Hormones (MIHs), and understanding how they initiate the largely conserved maturation process, remain important challenges. In hydrozoan cnidarians including the jellyfish Clytia hemisphaerica, MIH comprises neuropeptides released from somatic cells of the gonad. We identified the receptor (MIHR) for these MIH neuropeptides in Clytia using cell culture-based “deorphanization” of candidate oocyte-expressed GPCRs. MIHR mutant jellyfish generated using CRISPR-Cas9 had severe defects in gamete development or in spawning both in males and females. Female gonads, or oocytes isolated from MIHR mutants, failed to respond to synthetic MIH. Treatment with the cAMP analogue 5’Br-cAMP to mimic cAMP rise at maturation onset rescued meiotic maturation and spawning. Injection of inhibitory antibodies to GαS into wild type oocytes phenocopied the MIHR mutants. These results provide the molecular links between MIH stimulation and meiosis initiation in hydrozoan oocytes. Molecular phylogeny grouped Clytia MIHR with a subset of bilaterian neuropeptide receptors including Neuropeptide Y, Gonadotropin Inhibitory Hormone, pyroglutamylated RFamide and Luqin, all upstream regulators of sexual reproduction. This identification and functional characterisation of a cnidarian peptide GPCR advances our understanding of oocyte maturation initiation and sheds light on the evolution of neuropeptide-hormone systems.


2019 ◽  
Vol 2 (8) ◽  
pp. 3601-3606 ◽  
Author(s):  
Durga Dharmadana ◽  
Nicholas P. Reynolds ◽  
Charlotte E. Conn ◽  
Céline Valéry

2019 ◽  
Author(s):  
Alan V. Rincon ◽  
Tobias Deschner ◽  
Oliver Schülke ◽  
Julia Ostner

AbstractMammals living in stable social groups often mitigate the costs of group living through the formation of social bonds and cooperative relationships. The neuropeptide hormone oxytocin (OT) has been proposed to promote both bonding and cooperation although only a limited number of studies have investigated this under natural conditions. Our aim was to assess the role of OT in bonding and cooperation in male Barbary macaques (Macaca sylvanus). First we tested for an effect of affiliation - grooming and triadic male-infant-male interactions - with bond and non-bond partners on urinary OT levels. Secondly we aimed to test whether grooming interactions (and thus increased OT levels) increase a male’s general propensity to cooperate in polyadic conflicts. We collected behavioral data via full-day focal animal protocols on 14 adult males and measured endogenous OT levels from 139 urine samples collected after affiliation and non-social control periods. Urinary OT levels were higher after grooming with any partner. By contrast, OT levels after male-infant-male interactions with any partner or with bond partners were not different from controls but were higher after interactions with non-bond partners. Previous grooming did not increase the likelihood of males to support others in conflicts. Collectively, our results support research indicating that OT is involved in the regulation of adult social bonds, including in non-reproductive contexts. However, our male-infant-male interaction results go against previous studies suggesting that it is affiliation with bond rather than non-bond partners that trigger the release of OT. Alternatively, OT levels may have been elevated prior to male-infant-male interactions thus facilitating interaction between non-bond partners. The lack of an association of grooming (and by extension increased OT levels) and subsequent support speaks against an OT linked increase in the general propensity to cooperate, yet further studies are needed for a more direct test including the possibility of partner-specific contingent cooperation.


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