Neuropeptide derivatives to regulate the reproductive axis: Kisspeptin receptor (KISS1R) ligands and neurokinin‐3 receptor (NK3R) ligands

Oishi, Shinya; Fujii, Nobutaka

doi:10.1002/bip.22793

Cited by 3 publications

(1 citation statement)

References 74 publications

(85 reference statements)

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“…This receptor seems to be involved in the pathophysiology of some neurological disorders, such as epilepsy and schizophrenia [50,51]. In the hypothalamus, the neurokinin B is co-expressed with kisspeptin [52], a neuropeptide involved in 5-HT turnover stimulation [53]. Neurokinin B and kisspeptin showed also a cooperative mechanism at the neuroendocrine level [54], whereas the activation of NK3R triggered colon 5-HT release, especially in pro-inflammatory conditions [55].…”

Section: Discussionmentioning

confidence: 99%

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

Giacomo

Chiavaroli

Recinella

et al. 2020

IJMS

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Cannabidiol (CBD) and cannabigerol (CBG) are Cannabis sativa terpenophenols. Although CBD’s effectiveness against neurological diseases has already been demonstrated, nothing is known about CBG. Therefore, a comparison of the effects of these compounds was performed in two experimental models mimicking the oxidative stress and neurotoxicity occurring in neurological diseases. Rat astrocytes were exposed to hydrogen peroxide and cell viability, reactive oxygen species production and apoptosis occurrence were investigated. Cortexes were exposed to K+ 60 mM depolarizing stimulus and serotonin (5-HT) turnover, 3-hydroxykinurenine and kynurenic acid levels were measured. A proteomic analysis and bioinformatics and docking studies were performed. Both compounds exerted antioxidant effects in astrocytes and restored the cortex level of 5-HT depleted by neurotoxic stimuli, whereas sole CBD restored the basal levels of 3-hydroxykinurenine and kynurenic acid. CBG was less effective than CBD in restoring the levels of proteins involved in neurotransmitter exocytosis. Docking analyses predicted the inhibitory effects of these compounds towards the neurokinin B receptor. Conclusion: The results in the in vitro system suggest brain non-neuronal cells as a target in the treatment of oxidative conditions, whereas findings in the ex vivo system and docking analyses imply the potential roles of CBD and CBG as neuroprotective agents.

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Section: Discussionmentioning

confidence: 99%

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

Giacomo

Chiavaroli

Recinella

et al. 2020

IJMS

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Construction of an intranasal drug delivery system with hypothalamus‐targeting nanoparticles

Rao,

Xu,

Wang

et al. 2024

SusMat

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Dysfunction of the hypothalamus is associated with endocrine imbalances, growth abnormalities, and reproductive disorders. However, there is a lack of targeted treatment strategies focused on the hypothalamus. In this study, we constructed a multifunctional nanocarrier system (S@ANP) to directly target the hypothalamic neurokinin receptor 3 (NK3R) via an intranasal delivery strategy. This system could overcome the primary obstacles in drug delivery for hypothalamus‐related diseases. Under the guidance of a modified (Trp7, β‐Ala8)‐neurokinin A (4‐10) peptide with cysteine, nanoparticles encapsulated with SB222200, an NK3R inhibitor, were found to readily penetrate hypothalamic cells with substantial loading capacity, encapsulation efficiency, and sustained release in vitro. Moreover, intranasal delivery represents an optimal delivery strategy that allows for a significant reduction in oral dosage and enables nanoparticles to bypass the blood‒brain barrier and target relevant parts of the brain. The mucolytic agent N‐acetyl‐L‐cysteine (NAC) was loaded into the nanoparticles (S@ANP + NAC) to increase mucosal solubility and intranasal delivery efficiency. In vivo evaluations showed that S@ANP + NAC could effectively target the hypothalamus and modulate NK3R‐regulated hypothalamic functions in mice. Due to its high hypothalamic targeting efficiency and low toxicity, this intranasal nanoparticle drug delivery system may serve as a potential strategy for precision therapy of hypothalamic disorders.

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Peripheral action of kisspeptin at reproductive tissues—role in ovarian function and embryo implantation and relevance to assisted reproductive technology in livestock: a review

D’Occhio

Campanile

Baruselli

2020

Biology of Reproduction

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Kisspeptin (KISS1) is encoded by the KISS1 gene and was initially found to be a repressor of metastasis. Natural mutations in the KISS1 receptor gene (KISS1R) were subsequently shown be associated with idiopathic hypothalamic hypogonadism and impaired puberty. This led to interest in the role of KISS1 in reproduction. It was established that KISS1 had a fundamental role in the control of GnRH secretion. KISS1 neurons have receptors for leptin and estrogen receptor α (ERα) which places KISS1 at the gateway of metabolic (leptin) and gonadal (ERα) regulation of GnRH secretion. More recently, KISS1 has been shown to act at peripheral reproductive tissues. KISS1 and KISS1R genes are expressed in follicles (granulosa, theca, oocyte), trophoblast and uterus. KISS1 and KISS1R proteins are found in the same tissues. KISS1 appears to have autocrine and paracrine actions in follicle and oocyte maturation, trophoblast development, and implantation and placentation. In some studies, KISS1 was beneficial to in vitro oocyte maturation and blastocyst development. The next phase of KISS1 research will explore potential benefits on embryo survival and pregnancy. This will likely involve longer-term KISS1 treatments during proestrus, early embryo development, trophoblast attachment, and implantation and pregnancy. A deeper understanding of the direct action of KISS1 at reproductive tissues could help to achieve the next step change in embryo survival and improvement in the efficiency of assisted reproductive technology.

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Neuropeptide derivatives to regulate the reproductive axis: Kisspeptin receptor (KISS1R) ligands and neurokinin‐3 receptor (NK3R) ligands

Cited by 3 publications

References 74 publications

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

Antioxidant and Neuroprotective Effects Induced by Cannabidiol and Cannabigerol in Rat CTX-TNA2 Astrocytes and Isolated Cortexes

Construction of an intranasal drug delivery system with hypothalamus‐targeting nanoparticles

Peripheral action of kisspeptin at reproductive tissues—role in ovarian function and embryo implantation and relevance to assisted reproductive technology in livestock: a review

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