αCGRP, another amyloidogenic member of the CGRP family

Tsiolaki, Paraskevi L.; Nasi, Georgia I.; Baltoumas, Fotis A.; Louros, Nikolaos; Magafa, Vassiliki; Hamodrakas, Stavros J.; Iconomidou, Vassiliki A.

doi:10.1016/j.jsb.2018.02.008

Cited by 7 publications

(7 citation statements)

References 96 publications

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“…IA g7 is the only MHC class II molecule expressed in NOD mice. Like the highest T1D genetic risk factor, HLA-DQ8 and IA g7 shared a single polymorphism of a b57 in the b chain (5)(6)(7). The b57 polymorphism accounted for the pathogenic peptides that bind to these MHCIIs by breaking a stabilizing salt bridge to a76Arg in the MHCII a chain.…”

Section: Discussionmentioning

confidence: 99%

Calcitonin gene-related peptide is a potential autoantigen for CD4 T cells in type 1 diabetes

Wang

et al. 2022

Front. Immunol.

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The calcitonin gene-related peptide (CGRP) is a 37-amino acid neuropeptide with critical roles in the development of peripheral sensitization and pain. One of the CGRP family peptides, islet amyloid polypeptide (IAPP), is an important autoantigen in type 1 diabetes. Due to the high structural and chemical similarity between CGRP and IAPP, we expected that the CGRP peptide could be recognized by IAPP-specific CD4 T cells. However, there was no cross-reactivity between the CGRP peptide and the diabetogenic IAPP-reactive T cells. A set of CGRP-specific CD4 T cells was isolated from non-obese diabetic (NOD) mice. The T-cell receptor (TCR) variable regions of both α and β chains were highly skewed towards TRAV13 and TRBV13, respectively. The clonal expansion of T cells suggested that the presence of activated T cells responded to CGRP stimulation. None of the CGRP-specific CD4 T cells were able to be activated by the IAPP peptide. This established that CGRP-reactive CD4 T cells are a unique type of autoantigen-specific T cells in NOD mice. Using IAg7-CGRP tetramers, we found that CGRP-specific T cells were present in the pancreas of both prediabetic and diabetic NOD mice. The percentages of CGRP-reactive T cells in the pancreas of NOD mice were correlated to the diabetic progression. We showed that the human CGRP peptide presented by IAg7 elicited strong CGRP-specific T-cell responses. These findings suggested that CGRP is a potential autoantigen for CD4 T cells in NOD mice and probably in humans. The CGRP-specific CD4 T cells could be a unique marker for type 1 diabetes. Given the ubiquity of CGRP in nervous systems, it could potentially play an important role in diabetic neuropathy.

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Section: Discussionmentioning

confidence: 99%

Calcitonin gene-related peptide is a potential autoantigen for CD4 T cells in type 1 diabetes

Wang

et al. 2022

Front. Immunol.

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“…Therefore, we hypothesized whether high methylation of CpG island in the promoter region of CGRP gene in the umbilical cord tissues led to low expression of CGRP, promoting the development of preterm birth. The two subtypes of α CGRP and β CGRP have extremely high similarities and differ only in three amino acids, where one of them is lacking, and the other changes positively or negatively [ 30 , 31 ]. Compared with the wild-type control, the β CGRP mRNA levels in the dorsal root ganglia and spinal cord of α CGRP knockout mice showed no change, but the levels in the intestine were reduced by two times [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

DNA Methylation Pattern of CALCA and CALCB in Extremely Premature Infants with Monochorionic Triplets after Single‐Embryo Transfer

Gao

Guo

Chen

et al. 2021

Oxidative Medicine and Cellular Longevity

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Compared with full-term peers, premature infants are more likely to suffer from neonatal diseases and death. Variations in DNA methylation may affect these pathological processes. Calcitonin gene-related peptide (CGRP) plays a complex and diversified role in reproduction and chronic inflammation, and participates in the functional maintenance of vascular adaptation and trophoblast cells during pregnancy. Here, premature live births with single-chorionic triple embryos after single-embryo transfer were used as research objects, while full-term infants with double embryos and double-chorionic twins were used as controls. DNA was extracted from umbilical cord tissues for pyrosequencing to detect the methylation level of CpG island in CGRP promoter region. The average values of CGRP methylation in the umbilical cord tissues of very premature fetuses were higher than that of normal controls obtained from the databases. Immunofluorescence results showed that the expression of αCGRP was decreased in the blood vessel wall of the umbilical cord of monozygotic triplets, especially in death cases, while the βCGRP had a compensatory expression. In conclusion, our findings suggest that hypermethylation of CGRP might be considered as an important cause of serious neonatal morbidities.

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“…Specifically, the routine “Peptide docking” and its subroutine “multimer” were used to create our systems. The simulation boxes contained five (5) copies of each peptide-analogue in random conformations, previously shown to be an efficient number of copies for self-assembly simulations [ 36 , 37 ]. The generated clusters were evaluated with the balanced scoring scheme.…”

Section: Methodsmentioning

confidence: 99%

Bacterial Lectin FimH and Its Aggregation Hot-Spots: An Alternative Strategy against Uropathogenic Escherichia coli

et al. 2023

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Type I fimbriae are the main adhesive organelles of uropathogenic Escherichia coli (UPEC), consisting of four different subunits. Their component with the most important role in establishing bacterial infections is the FimH adhesin located at the fimbrial tip. This two-domain protein mediates adhesion to host epithelial cells through interaction with terminal mannoses on epithelial glycoproteins. Here, we propose that the amyloidogenic potential of FimH can be exploited for the development of therapeutic agents against Urinary Tract Infections (UTIs). Aggregation-prone regions (APRs) were identified via computational methods, and peptide-analogues corresponding to FimH lectin domain APRs were chemically synthesized and studied with the aid of both biophysical experimental techniques and molecular dynamic simulations. Our findings indicate that these peptide-analogues offer a promising set of antimicrobial candidate molecules since they can either interfere with the folding process of FimH or compete for the mannose-binding pocket.

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αCGRP, another amyloidogenic member of the CGRP family

Cited by 7 publications

References 96 publications

Calcitonin gene-related peptide is a potential autoantigen for CD4 T cells in type 1 diabetes

Calcitonin gene-related peptide is a potential autoantigen for CD4 T cells in type 1 diabetes

DNA Methylation Pattern of CALCA and CALCB in Extremely Premature Infants with Monochorionic Triplets after Single‐Embryo Transfer

Bacterial Lectin FimH and Its Aggregation Hot-Spots: An Alternative Strategy against Uropathogenic Escherichia coli

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