The role for IGF-1-derived small neuropeptides as a therapeutic target for neurological disorders

Guan, Jian; Harris, Patricia M.; Brimble, Margaret A.; Yang, Lei; Lü, Jun; Yang, Yang; Gunn, Alistair J.

doi:10.1517/14728222.2015.1010514

Cited by 45 publications

(35 citation statements)

References 69 publications

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“…However, since GPE has an extremely short mean-life in vivo, further studies will be necessary to investigate whether the GPE analogues with longer half-lives that are currently being tested in clinical trials [34] show similar effects on cell proliferation and migration. In addition, the effects of novel IGF-I-derived smaller peptides are now being studied in human patients [35]. …”

Section: Discussionmentioning

confidence: 99%

GPE Promotes the Proliferation and Migration of Mouse Embryonic Neural Stem Cells and Their Progeny In Vitro

Almengló

Devesa²,

Devesa³

et al. 2017

IJMS

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This study was designed to investigate a possible role of the N-terminal tripeptide of insulin-like growth factor-1 (IGF-I), Gly-Pro-Glu (GPE), physiologically generated in neurons following IGF-I-specific cleavage, in promoting neural regeneration after an injury. Primary cultures of mouse neural stem cells (NSCs), obtained from 13.5 Days post-conception (dpc) mouse embryos, were challenged with either GPE, growth hormone (GH), or GPE + GH and the effects on cell proliferation, migration, and survival were evaluated both under basal conditions and in response to a wound healing assay. The cellular pathways activated by GPE were also investigated by using specific chemical inhibitors. The results of the study indicate that GPE treatment promotes the proliferation and the migration of neural stem cells in vitro through a mechanism that involves the activation of extracellular signal-regulated kinase (ERK) and phosphoinositide 3-kinase PI3K-Akt pathways. Intriguingly, both GPE effects and the signaling pathways activated were similar to those observed after GH treatment. Based upon the results obtained from this study, GPE, as well as GH, may be useful in promoting neural protection and/or regeneration after an injury.

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Section: Discussionmentioning

confidence: 99%

GPE Promotes the Proliferation and Migration of Mouse Embryonic Neural Stem Cells and Their Progeny In Vitro

Almengló

Devesa²,

Devesa³

et al. 2017

IJMS

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“…Based on nuclear magnetic resonance spectroscopy, it was reported that the chemical shift between γ and β of the prolyl residue in the trans conformation (80% isoforms) is about 5 ppm, which promotes the formation of a cGP. Cyclization protects the molecule against the enzymatic hydrolysis and increases its lipophilic properties. cGP as a small molecule (192 Da) is able to cross the blood–brain barrier and exert biological effects in the CNS.…”

Section: Igf‐1‐derived Cgp and Its Generationmentioning

confidence: 99%

Proline‐containing peptides—New insight and implications: A Review

Misiura

Miltyk

2019

BioFactors

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The family of regulatory proline‐containing peptides (PCPs), also known as glyprolines, exhibit significant biological activity. The group of glyprolines includes Gly‐Pro (GP), Pro‐Gly‐Pro (PGP), cyclic Gly‐Pro (cGP), as well as PGP derivatives, for example, N‐acetylated PGP (N‐a‐PGP) and N‐methylated PGP (N‐m‐PGP). PCPs are engaged in various biological processes including the proinflammatory neutrophil chemoattraction in lung diseases, inflammatory bowel diseases or ischemic stroke. Glyprolines have been also postulated to play an important role as atheroprotective and anticoagulant agents, exhibit neuroprotective effects in Parkinson's disease, as well as regulate insulin‐like growth factor (IGF) homeostasis. It was also noticed that PCPs inhibit proliferation and migration of keratinocytes in wound healing, protection of the gastric mucosa and stimulation of its regeneration. The regulatory glyprolines are derived from endogenous and exogenous sources. Most PCPs are derived from collagen or diet protein degradation. Recently, great interest is concentrated on short proline‐rich oligopeptides derived from IGF‐1 degradation. The mechanism of PCPs biological activity is not fully explained. It involves receptor‐mediated mechanisms, for example, N‐a‐PGP acts as CXCR1/2 receptor ligand, whereas cGP regulates IGF‐1 bioavailability by modifying the IGF‐1 binding to the IGF‐1 binding protein‐3. PGP has been observed to interact with collagen‐specific receptors. The data suggest a promising role of PGP as a target of various diseases therapy. This review is focused on the effect of PCPs on metabolic processes in different tissues and the molecular mechanism of their action as an approach to pharmacotherapy of PCPs‐dependent diseases.

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“…Cyclic‐glycine‐proline (cGP) is produced from the cyclization of the N‐terminal tripeptide of IGF‐1, glycine‐proline‐glutamate (GPE), when IGF‐1 is enzymatically broken down to GPE and des(1‐3)IGF1 (reviewed in Guan et al, ). Endogenous cGP is present in rat milk, with higher concentrations during peak lactation compared with late lactation/early involution (Singh‐Mallah et al, ).…”

Section: Introductionmentioning

confidence: 99%

“…For instance, cGP is shown to inhibit or promote IGF‐1 function under pathological conditions when IGF‐1 function is relatively increased or diminished, respectively (Guan et al, ). Previous studies have only investigated the roles of cGP in brain development and functional recovery from brain injuries (Guan et al, ; Guan, Zhang, Dale‐Gandar, Hodgkinson, & Vickers, ; Guan et al, ; Gudasheva et al, , Gudasheva et al, ; Singh‐Mallah et al, ), with one study showing the efficacy of cGP in inhibiting IGF‐1‐dependent tumour growth (Guan et al, ). However, the role of cGP in mammary involution, more specifically, in modulating the physiological changes in IGF‐1 function during involution, is not known.…”

Section: Introductionmentioning

confidence: 99%

Cyclic‐glycine‐proline accelerates mammary involution by promoting apoptosis and inhibiting IGF‐1 function

Singh-Mallah

McMahon

Guan

et al. 2017

Journal Cellular Physiology

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In rodents, post-lactational involution of mammary glands is characterized by the loss of mammary epithelial cells via apoptosis, which is associated with a decline in the expression of insulin-like growth factor-1 (IGF-1). Overexpression of IGF-1 delays involution by inhibiting apoptosis of epithelial cells and preserving the remaining secretory alveoli. Cyclic-glycine-proline (cGP), a metabolite of IGF-1, normalizes IGF-1 function under pathological conditions by regulating the bioavailability of IGF-1. The present study investigated the effect of cGP on the physiological decline in IGF-1 function during post-lactational mammary involution. Rat dams were gavaged with either cGP (3 mg/kg) or saline once per day from post-natal d8-22. Before collecting tissue on post-natal d23, a pair of mammary glands were sealed on d20 (72 hr-engorgement, thus representative of late-involution) and d22 (24 hr-engorgement, thus representative of mid-involution), while the remaining glands were allowed to involute naturally (early-involution). During early-involution, cGP accelerated the loss of mammary cells through apoptosis, resulting in an earlier clearance of intact secretory alveoli compared with the control group. This coincided with an earlier up-regulation of the cell survival factors, Bcl-xl and IGF-1R, in the early-involution cGP glands compared with the control glands. During late-involution, cGP reduced the bioactivity of IGF-1, which was evident through decreased phosphorylation of IGF-1R in the regressed alveoli. Maternal administration of cGP did not alter milk production and composition during early-, peak-, or late-stage of lactation. These data show that cGP accelerates post-lactational involution by promoting apoptosis and the physiological decline in IGF-1 function.

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The role for IGF-1-derived small neuropeptides as a therapeutic target for neurological disorders

Cited by 45 publications

References 69 publications

GPE Promotes the Proliferation and Migration of Mouse Embryonic Neural Stem Cells and Their Progeny In Vitro

GPE Promotes the Proliferation and Migration of Mouse Embryonic Neural Stem Cells and Their Progeny In Vitro

Proline‐containing peptides—New insight and implications: A Review

Cyclic‐glycine‐proline accelerates mammary involution by promoting apoptosis and inhibiting IGF‐1 function

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