QRFP administration into the medial hypothalamic nuclei improves memory in rats

Zagoracz, Olga; Ollmann, Tamás; Péczely, László; László, Kristóf; Kovács, Anita; Berta, Balázs; Kállai, Veronika; Kertes, Erika; Lénárd, László

doi:10.1016/j.brainres.2019.146563

Cited by 4 publications

(36 citation statements)

References 35 publications

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“…In humans, both 26RFa-and 43RFa-immunoreactive forms have been detected in hypothalamic and spinal cord extracts [9]. Interestingly, the presence of a tribasic cleavage site (Arg-Lys-Arg/Lys) within the 26RFa sequence suggests that the C-terminal heptapeptide GGFSFRF-NH 2 , named 26RFa (20)(21)(22)(23)(24)(25)(26) , could also be produced from the precursor. However, to date, this fragment, whose sequence is highly conserved in tetrapods, has not been identified as a mature product of the 26RFa/QRFP gene transcription.…”

Section: Introductionmentioning

confidence: 99%

“…named 26RFa (20)(21)(22)(23)(24)(25)(26), could also be produced from the precursor. However, to date, this fragment, whose sequence is highly conserved in tetrapods, has not been identified as a mature product of the 26RFa/QRFP gene transcription.…”

Section: Introductionmentioning

confidence: 99%

“…In contrast, the residues of the -Phe 24 -Arg 25 -Phe 26 -NH2 triad are very sensitive to substitutions and only tolerate subtle amendments for improving bioactivity like the ω-methylation of arginine 25 [38]. To date, few replacements have been reported in the phenylalanine positions of 26RFa (20)(21)(22)(23)(24)(25)(26) [5]. As previously suggested for PrRP and kisspeptin [40], our work emphasizes that optimized modifications in the C-terminal part of 26RFa are mandatory to design selective and potent peptidergic ligands for hQRFPR.…”

Section: Introductionmentioning

confidence: 99%

“…However, 26RFa can be downsized from the N-terminal extremity with a gradual decrease in its ability to mobilize intracellular calcium concentration ([Ca 2+ ] i ) in CHO cells transfected by the human QRFPR (hQRFPR) [36]. Since 26RFa (20)(21)(22)(23)(24)(25)(26) (LV-2021) mimics the orexigenic and gonadotropic effects of full-length 26RFa [12,17], it appears that this C-terminal heptapeptide can serve as a molecular scaffold for designing low molecular weight, potent and stable hQRFPR ligands. As a matter of fact, 26RFa (20)(21)(22)(23)(24)(25)(26) has already been successfully used to design nanomolar active agonists such as [Nva 23 ]26RFa (20)(21)(22)(23)(24)(25)(26) (LV-2073) [36], [Cmpi 21 , aza-β 3 -Hht 23 ]26RFa (21)(22)(23)(24)(25)(26) (LV-2172) [37], and [(Me) ω Arg 25 ]26RFa (20)(21)(22)(23)(24)(25)(26) (LV-2186) [38], as well as proteolytic resistant pseudopeptides (Figure 2) [39].…”

Section: Introductionmentioning

confidence: 99%

“…Since 26RFa (20)(21)(22)(23)(24)(25)(26) (LV-2021) mimics the orexigenic and gonadotropic effects of full-length 26RFa [12,17], it appears that this C-terminal heptapeptide can serve as a molecular scaffold for designing low molecular weight, potent and stable hQRFPR ligands. As a matter of fact, 26RFa (20)(21)(22)(23)(24)(25)(26) has already been successfully used to design nanomolar active agonists such as [Nva 23 ]26RFa (20)(21)(22)(23)(24)(25)(26) (LV-2073) [36], [Cmpi 21 , aza-β 3 -Hht 23 ]26RFa (21)(22)(23)(24)(25)(26) (LV-2172) [37], and [(Me) ω Arg 25 ]26RFa (20)(21)(22)(23)(24)(25)(26) (LV-2186) [38], as well as proteolytic resistant pseudopeptides (Figure 2) [39]. According to our previous structure-activity relationship studies [for review, 5], these compounds exhibit modifications at positions occupied by residues classified as permissive to substitution or engaged in peptide bonds susceptible to degradation.…”

Section: Introductionmentioning

confidence: 99%

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Point-Substitution of Phenylalanine Residues of 26RFa Neuropeptide: A Structure-Activity Relationship Study

et al. 2021

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26RFa is a neuropeptide that activates the rhodopsin-like G protein-coupled receptor QRFPR/GPR103. This peptidergic system is involved in the regulation of a wide array of physiological processes including feeding behavior and glucose homeostasis. Herein, the pharmacological profile of a homogenous library of QRFPR-targeting peptide derivatives was investigated in vitro on human QRFPR-transfected cells with the aim to provide possible insights into the structural determinants of the Phe residues to govern receptor activation. Our work advocates to include in next generations of 26RFa(20–26)-based QRFPR agonists effective substitutions for each Phe unit, i.e., replacement of the Phe22 residue by a constrained 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid moiety, and substitution of both Phe24 and Phe26 by their para-chloro counterpart. Taken as a whole, this study emphasizes that optimized modifications in the C-terminal part of 26RFa are mandatory to design selective and potent peptide agonists for human QRFPR.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Point-Substitution of Phenylalanine Residues of 26RFa Neuropeptide: A Structure-Activity Relationship Study

et al. 2021

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Potentials of Neuropeptides as Therapeutic Agents for Neurological Diseases

Yeo

Cunliffe

et al. 2022

Biomedicines

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Despite recent leaps in modern medicine, progress in the treatment of neurological diseases remains slow. The near impermeable blood-brain barrier (BBB) that prevents the entry of therapeutics into the brain, and the complexity of neurological processes, limits the specificity of potential therapeutics. Moreover, a lack of etiological understanding and the irreversible nature of neurological conditions have resulted in low tolerability and high failure rates towards existing small molecule-based treatments. Neuropeptides, which are small proteinaceous molecules produced by the body, either in the nervous system or the peripheral organs, modulate neurological function. Although peptide-based therapeutics originated from the treatment of metabolic diseases in the 1920s, the adoption and development of peptide drugs for neurological conditions are relatively recent. In this review, we examine the natural roles of neuropeptides in the modulation of neurological function and the development of neurological disorders. Furthermore, we highlight the potential of these proteinaceous molecules in filling gaps in current therapeutics.

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Brain RFamide Neuropeptides in Stress-Related Psychopathologies

Kovács,

Szabó,

László

et al. 2024

Cells

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The RFamide peptide family is a group of proteins that share a common C-terminal arginine–phenylalanine–amide motif. To date, the family comprises five groups in mammals: neuropeptide FF, LPXRFamides/RFamide-related peptides, prolactin releasing peptide, QRFP, and kisspeptins. Different RFamide peptides have their own cognate receptors and are produced by different cell populations, although they all can also bind to neuropeptide FF receptors with different affinities. RFamide peptides function in the brain as neuropeptides regulating key aspects of homeostasis such as energy balance, reproduction, and cardiovascular function. Furthermore, they are involved in the organization of the stress response including modulation of pain. Considering the interaction between stress and various parameters of homeostasis, the role of RFamide peptides may be critical in the development of stress-related neuropathologies. This review will therefore focus on the role of RFamide peptides as possible key hubs in stress and stress-related psychopathologies. The neurotransmitter coexpression profile of RFamide-producing cells is also discussed, highlighting its potential functional significance. The development of novel pharmaceutical agents for the treatment of stress-related disorders is an ongoing need. Thus, the importance of RFamide research is underlined by the emergence of peptidergic and G-protein coupled receptor-based therapeutic targets in the pharmaceutical industry.

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QRFP administration into the medial hypothalamic nuclei improves memory in rats

Cited by 4 publications

References 35 publications

Point-Substitution of Phenylalanine Residues of 26RFa Neuropeptide: A Structure-Activity Relationship Study

Point-Substitution of Phenylalanine Residues of 26RFa Neuropeptide: A Structure-Activity Relationship Study

Potentials of Neuropeptides as Therapeutic Agents for Neurological Diseases

Brain RFamide Neuropeptides in Stress-Related Psychopathologies

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