The Biological Role of Truncated Insulin‐like Growth Factor‐1 and the Tripeptide GPE in the Central Nervous System<sup>a</sup>

Sara, Vicki R.; Carlsson-Skwirut, Christine; Drakenberg, Katarina; Giacobini, MaiBritt; L, Håkansson; Mirmiran, M.; Nordberg, Agneta; Olson, Lar̀s; Reinecke, Manfred; Ståhlbom, P. A.; Nordqvist, A. C. Sandberg

doi:10.1111/j.1749-6632.1993.tb26216.x

Cited by 58 publications

(43 citation statements)

References 37 publications

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“…The mature peptide comprises four domains, that is, the B amino-terminal domain, C and A domain and D carboxyterminal domain, of IGF-I polypeptides (25,84). In addition, two other protein products have been identified in the human brain; the tripeptide glycylprolyl-glutamate (GPE) corresponding to the NH 2 -terminal of the B domain of mature IGF-I and a truncated IGF-I form (-3N:IGF-I) that lacks the first three amino acids of the amino terminal end of mature peptide, probably due to alternate signal peptides or the combined action of some peptidases (78,85,86). Removal of the NH 2 -terminal tripeptide could be a mechanism for increasing the biological potency and availability of IGF-I, since the truncated -3N:IGF-I has less affinity for IGF-binding proteins than mature IGF-I, thus, increasing its bioactivity (78), (see Figure 1A) (see below: IGF-I Receptors and Binding Proteins).…”

Section: Igf-i Processing Secretion and Glycosylationmentioning

confidence: 99%

The Complexity of the IGF1 Gene Splicing, Posttranslational Modification and Bioactivity

Philippou

Maridaki

Pneumaticos

et al. 2014

Mol Med

100

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The insulinlike growth factor-I (IGF-I) is an important factor which regulates a variety of cellular responses in multiple biological systems. The IGF1 gene comprises a highly conserved sequence and contains six exons, which give rise to heterogeneous mRNA transcripts by a combination of multiple transcription initiation sites and alternative splicing. These multiple transcripts code for different precursor IGF-I polypeptides, namely the IGF-IEa, IGF-IEb and IGF-IEc isoforms in humans, which also undergo posttranslational modifications, such as proteolytic processing and glycosylation. IGF-I actions are mediated through its binding to several cell-membrane receptors and the IGF-I domain responsible for the receptor binding is the bioactive mature IGF-I peptide, which is derived after the posttranslational cleavage of the pro-IGF-I isoforms and the removal of their carboxy-terminal E-peptides (that is, the Ea, Eb and Ec). Interestingly, differential biological activities have been reported for the different IGF-I isoforms, or for their E-peptides, implying that IGF-I peptides other than the IGF-I ligand also possess bioactivity and, thus, both common and unique or complementary pathways exist for the IGF-I isoforms to promote biological effects. The multiple peptides derived from IGF-I and the differential expression of its various transcripts in different conditions and pathologies appear to be compatible with the distinct cellular responses observed to the different IGF-I peptides and with the concept of a complex and possibly isoform-specific IGF-I bioactivity. This concept is discussed in the present review, in the context of the broad range of modifications that this growth factor undergoes which might regulate its mechanism(s) of action.

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Section: Igf-i Processing Secretion and Glycosylationmentioning

confidence: 99%

The Complexity of the IGF1 Gene Splicing, Posttranslational Modification and Bioactivity

Philippou

Maridaki

Pneumaticos

et al. 2014

Mol Med

100

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“…NNZ-2566 is a synthetic analogue of the tripeptide (1-3)IGF-1, which is produced when the full-length IGF-1 polypeptide is cleaved in the brain [94]. Although the mechanisms of action of (1-3)IGF-1 and intact IGF-1 are different, [95], they are both important in glutamatergic synapse formation [96].…”

Section: Treatment Implicationsmentioning

confidence: 99%

Phelan–McDermid Syndrome and SHANK3: Implications for Treatment

2015

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“…[1][2][3][4][5][6] Preclinical studies over the past decade have demonstrated that IGF-1 can protect against neuronal and glial cell degeneration in animal models of stroke such as hypoxia-ischemia. 7,8 Although the results to date are encouraging, the size of the IGF-1 molecule has proved problematic and has led researchers to investigate routes of administration that bypass the blood-brain barrier, such as intranasal application, or to focus on fragments of IGF-1, such as the N-terminal peptide Gly-Pro-Glu (GPE).…”

mentioning

confidence: 99%

Combining Insulin-Like Growth Factor Derivatives Plus Caffeinol Produces Robust Neuroprotection After Stroke in Rats

Zhao

Liu

Zhang

et al. 2005

Stroke

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Background and Purpose-Insulin-like growth factor-1 (IGF-1) and caffeinol are both neuroprotective and probably have different mechanisms of action; therefore, they may be more effective in combination. Methods-We tested the N-terminal tripeptide of IGF-1, Gly-Pro-Glu (GPE), and its analogue, G2MePE, alone and with caffeinol in a rat middle cerebral artery (MCA) suture occlusion model. We randomly assigned rats to 6 groups of 8 to 12 animals: (1) control; (2) GPE, 3 mg/kg per hour; (3) G2MePE, 0.3 mg/kg per hour; (4) caffeinol, a mixture of caffeine (10 mg/kg) with ethanol (0.32 g/kg); (5) GPE with caffeinol (combination of group 2 with 4); and (6)

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The Biological Role of Truncated Insulin‐like Growth Factor‐1 and the Tripeptide GPE in the Central Nervous System^a

Cited by 58 publications

References 37 publications

The Complexity of the IGF1 Gene Splicing, Posttranslational Modification and Bioactivity

The Complexity of the IGF1 Gene Splicing, Posttranslational Modification and Bioactivity

Phelan–McDermid Syndrome and SHANK3: Implications for Treatment

Combining Insulin-Like Growth Factor Derivatives Plus Caffeinol Produces Robust Neuroprotection After Stroke in Rats

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The Biological Role of Truncated Insulin‐like Growth Factor‐1 and the Tripeptide GPE in the Central Nervous Systema

Cited by 58 publications

References 37 publications

The Complexity of the IGF1 Gene Splicing, Posttranslational Modification and Bioactivity

The Complexity of the IGF1 Gene Splicing, Posttranslational Modification and Bioactivity

Phelan–McDermid Syndrome and SHANK3: Implications for Treatment

Combining Insulin-Like Growth Factor Derivatives Plus Caffeinol Produces Robust Neuroprotection After Stroke in Rats

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Product

Resources

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The Biological Role of Truncated Insulin‐like Growth Factor‐1 and the Tripeptide GPE in the Central Nervous System^a