Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Insulin-Like Growth Factors in the Pathogenesis of Neurological Diseases in Children.

ABSTRACT: Insulin-like growth factors play a key role for neuronal growth, differentiation, the survival of neurons and synaptic formation. The action of IGF-1 is most pronounced in the developing brain. In this paper we will try to give an answer to the following questions: Why are studies in children important? What clinical studies in neonatal asphyxia, infantile spasms, progressive encephalopathy-hypsarrhythmia-optical atrophy (PEHO) syndrome, infantile ceroid lipofuscinosis (INCL), autistic spectrum disorders (ASD) and subacute sclerosing encephalopathy (SSPE) have been carried out? What are IGF-based therapeutic strategies? What are the therapeutic approaches? We conclude that there are now great hopes for the therapeutic use of IGF-1 for some neurological disorders (particularly ASD).

SUBMITTER: Riikonen R

PROVIDER: S-EPMC5666738 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Insulin-Like Growth Factors in the Pathogenesis of Neurological Diseases in Children.

Riikonen Raili R

International journal of molecular sciences 20170926 10

Insulin-like growth factors play a key role for neuronal growth, differentiation, the survival of neurons and synaptic formation. The action of IGF-1 is most pronounced in the developing brain. In this paper we will try to give an answer to the following questions: Why are studies in children important? What clinical studies in neonatal asphyxia, infantile spasms, progressive encephalopathy-hypsarrhythmia-optical atrophy (PEHO) syndrome, infantile ceroid lipofuscinosis (INCL), autistic spectrum ...[more]

PMID: 28954393

Similar Datasets

Mitochondrial protein dysfunction in pathogenesis of neurological diseases.

Project description:Mitochondria are essential organelles for neuronal function and cell survival. Besides the well-known bioenergetics, additional mitochondrial roles in calcium signaling, lipid biogenesis, regulation of reactive oxygen species, and apoptosis are pivotal in diverse cellular processes. The mitochondrial proteome encompasses about 1,500 proteins encoded by both the nuclear DNA and the maternally inherited mitochondrial DNA. Mutations in the nuclear or mitochondrial genome, or combinations of both, can result in mitochondrial protein deficiencies and mitochondrial malfunction. Therefore, mitochondrial quality control by proteins involved in various surveillance mechanisms is critical for neuronal integrity and viability. Abnormal proteins involved in mitochondrial bioenergetics, dynamics, mitophagy, import machinery, ion channels, and mitochondrial DNA maintenance have been linked to the pathogenesis of a number of neurological diseases. The goal of this review is to give an overview of these pathways and to summarize the interconnections between mitochondrial protein dysfunction and neurological diseases.

| S-EPMC9489860 | biostudies-literature

Personalised medicine in paediatrics: individualising treatment in children with rare neurological diseases.

Project description:The development of personalised medicine is of considerable importance for paediatric patient populations, and represents a move away from the use of treatment dosages based on experience with the same compounds in adults. Currently, however, we know little about developmental pharmacogenomics and, although many biomarkers are available for clinical research use, there have been few applications in the management of paediatric diseases. This paper reviews where we are in the journey towards achieving paediatric personalised medicine and describes a group of diseases requiring such an approach. The personalised medicine approach is particularly relevant for the treatment of rare childhood diseases, and the group of life-threatening neurological disorders known as lysosomal storage diseases represents a potential study population. The genetic bases of these disorders are generally well defined, there is the potential for diagnosis at birth or prenatally, and there are a range of therapeutic options available or under development.

| S-EPMC3405387 | biostudies-other

Factors Associated with Mutations: Their Matching Rates to Cardiovascular and Neurological Diseases.

Project description:Monogenic hypertension is rare and caused by genetic mutations, but whether factors associated with mutations are disease-specific remains uncertain. Given two factors associated with high mutation rates, we tested how many previously known genes match with (i) proximity to telomeres or (ii) high adenine and thymine content in cardiovascular diseases (CVDs) related to vascular stiffening. We extracted genomic information using a genome data viewer. In human chromosomes, 64 of 79 genetic loci involving >25 rare mutations and single nucleotide polymorphisms satisfied (i) or (ii), resulting in an 81% matching rate. However, this high matching rate was no longer observed as we checked the two factors in genes associated with essential hypertension (EH), thoracic aortic aneurysm (TAA), and congenital heart disease (CHD), resulting in matching rates of 53%, 70%, and 75%, respectively. A matching of telomere proximity or high adenine and thymine content projects the list of loci involving rare mutations of monogenic hypertension better than those of other CVDs, likely due to adoption of rigorous criteria for true-positive signals. Our data suggest that the factor-disease matching rate is an accurate tool that can explain deleterious mutations of monogenic hypertension at a >80% match-unlike the relatively lower matching rates found in human genes of EH, TAA, CHD, and familial Parkinson's disease.

| S-EPMC8151074 | biostudies-literature

Concentrations of Insulin-like Growth Factors and Insulin-like Growth Factor-Binding Proteins and Respective Gene Expressions in Children before and after Hematopoietic Stem Cell Transplantation.

Project description:Insulin-like growth factors (IGF-1 and IGF-2) and insulin-like growth factor-binding proteins (IGFBP-1 to -7) are involved in the regulation of cell proliferation and differentiation and may be associated with various metabolic parameters. The aim of our study was to compare levels of IGFs and IGFBPs and the expressions of their genes in children before and after hematopoietic stem cell transplantation (HSCT) to assess their potential as markers of late metabolic complications of HSCT. We also conducted additional comparisons with healthy controls and of correlations of IGF and IGFBP levels with anthropometric and biochemical parameters. We analyzed 19 children treated with HSCT and 21 healthy controls. We found no significant differences in the levels of IGFs and IGFBPs and expressions of their genes before and after HSCT, while IGF and IGFBP levels were significantly lower in children treated with HSCT compared with controls. We conclude that our results did not reveal significant differences between the levels of IGFs and IGFBPs before and after HSCT, which would make them obvious candidates for markers of late complications of the procedure in children. However, due to the very low number of patients this conclusion must be taken with caution and may be altered by further research.

| S-EPMC8709367 | biostudies-literature

Association of insulin and insulin-like growth factors with Barrett's oesophagus.

Project description:BACKGROUND:It is postulated that high serum levels of insulin and insulin growth factor 1 (IGF-1) mediate obesity-associated carcinogenesis. The relationship of insulin, IGF-1 and IGF binding proteins (IGFBP) with Barrett's oesophagus (BO) has not been well examined. METHODS:Serum levels of insulin and IGFBPs in patients with BO were compared with two separate control groups: subjects with gastro-oesophageal reflux disease (GORD) and screening colonoscopy controls. Fasting insulin, IGF-1 and IGFBPs were assayed in the serum of BO cases (n = 135), GORD (n = 135) and screening colonoscopy (n = 932) controls recruited prospectively at two academic hospitals. Logistic regression was used to estimate the risk of BO. RESULTS:Patients in the highest tertile of serum insulin levels had an increased risk of BO compared with colonoscopy controls (adjusted OR 2.02, 95% CI 1.15 to 3.54) but not compared with GORD controls (adjusted OR 1.55, 95% CI 0.76 to 3.15). Serum IGF-1 levels in the highest tertile were associated with an increased risk of BO (adjusted OR 4.05, 95% CI 2.01 to 8.17) compared with the screening colonoscopy control group but were not significantly different from the GORD control group (adjusted OR 0.57, 95% CI 0.27 to 1.17). IGFBP-1 levels in the highest tertile were inversely associated with a risk of BO in comparison with the screening colonoscopy controls (adjusted OR 0.11, 95% CI 0.05 to 0.24) but were not significantly different from the GORD control group (adjusted OR 1.04, 95% CI 0.49 to 2.16). IGFBP-3 levels in the highest tertile were inversely associated with the risk of BO compared with the GORD controls (OR 0.36, 95% CI 0.16 to 0.81) and also when compared with the colonoscopy controls (OR 0.40, 95% CI 0.20 to 0.79). CONCLUSIONS:These results provide support for the hypothesis that the insulin/IGF signalling pathways have a role in the development of BO.

| S-EPMC3669672 | biostudies-literature

Clinical Experience of Neurological Mitochondrial Diseases in Children and Adults: A Single-Center Study.

Project description:The goal of the study was to retrospectively evaluate a cohort of children and adults with mitochondrial diseases (MDs) in a single-center experience. Neurological clinical examination, brain magnetic resonance imaging (MRI) and spectroscopy, muscle biopsy, metabolic and molecular-genetic analysis were evaluated in 26 children and 36 adult patients with MD in Slovenia from 2004 to 2018. Nijmegen MD criteria (MDC) were applied to all patients and the need for a muscle biopsy was estimated. Exome-sequencing was used in half of the patients. Twenty children (77.0%) and 12 adults (35.0%) scored a total of ≥8 on MDC, a result that is compatible with the diagnosis of definite MD. Yield of exome-sequencing was 7/22 (31.0%), but the method was not applied systematically in all patients from the beginning of diagnostics. Brain MRI morphological changes, which can be an imaging clue for the diagnosis of MD, were found in 17/24 children (71.0%). In 7/26 (29.0%) children, and in 20/30 (67.0%) adults, abnormal mitochondria were found on electron microscopy (EM) and ragged-red fibers were found in 16/30 (53.0%) adults. Respiratory chain enzymes (RCEs) and/or pyruvate dehydrogenase complex (PDHc) activities were abnormal in all the children and six adult cases. First, our data revealed that MDC was useful in the clinical diagnosis of MD, and second, until the use of NGS methods, extensive, laborious and invasive diagnostic procedures were performed to reach a final diagnosis. In patients with suspected MD, there is a need to prioritize molecular diagnosis with the more modern next-generation sequencing (NGS) method.

| S-EPMC9524181 | biostudies-literature

The proliferating role of insulin and insulin-like growth factors in cancer.

Project description:Epidemiological studies have reported an increased risk of cancer in people with type 2 diabetes (T2DM) and obesity, related in part to hyperinsulinemia, secondary to insulin resistance. Hyperinsulinemia leads to increased expression of insulin-like growth factor (IGF)-I expression. In fact, increased insulin, IGF-I and IGF-II levels are associated with tumor growth in vitro, in animal models, and in epidemiological studies in humans. In this paper, we discuss the roles of insulin, IGF-I and IGF-II, their interaction with the insulin receptor (IR) and IGF-I receptor (IGF-IR), and their signaling pathways and regulation as these pertain to tumor growth. We explain how these pathways have been deciphered by in vitro and in vivo studies, and how they are being exploited in the development of targeted cancer therapies.

| S-EPMC2949481 | biostudies-literature

Associations of lifestyle factors with serum dehydroepiandrosterone sulphate and insulin-like growth factor-1 concentration in prepubertal children.

Project description:OBJECTIVE:Little is known about the relationships of dietary factors, physical activity and sedentary behaviour to dehydroepiandrosterone sulphate (DHEAS) and insulin-like growth factor-1 (IGF-1) concentrations among prepubertal children. Therefore, we studied the associations of these lifestyle factors with serum DHEAS and IGF-1 in children. DESIGN AND SUBJECTS:Cross-sectional analysis of a population sample of 431 prepubertal children aged 6-9 years. MEASUREMENTS:Assessment of dietary factors by food records and physical activity and sedentary behaviour by a combined heart rate and movement monitor and a questionnaire. Measurement of serum DHEAS and IGF-1. RESULTS:Consumption of low-fibre grain products (standardized regression coefficient ? = .118, P = .017) and intake of vegetable protein (? = .100, P = .045) was positively and consumption of sugar-sweetened beverages (? = -.117, P = .018) was inversely associated with DHEAS after adjustment for sex, age and body fat percentage. Energy intake (? = .160, P = .001) was positively associated with IGF-1 adjusting for sex, age and body fat percentage. Vigorous physical activity was inversely associated with DHEAS after adjustment for sex and age (? = -.120, P = .027), and total (? = -.137, P = .007), moderate (? = -.130, P = .012), vigorous (? = -.136, P = .011) and moderate to vigorous physical activity (? = -.160, P = .003) were inversely and total sedentary behaviour (? = .151, P = .003) was positively associated with IGF-1 adjusting for sex and age. None of physical activity measures was associated with DHEAS or IGF-1 after additional adjustment for body fat percentage. CONCLUSIONS:Lifestyle factors have weak and moderate associations with biochemical markers of adrenarche in prepubertal children. These associations indicate body fat independent and dependent influences of diet and physical activity, respectively.

| S-EPMC6195184 | biostudies-literature

Structural basis for the inhibition of insulin-like growth factors by insulin-like growth factor-binding proteins.

Project description:Insulin-like growth factor-binding proteins (IGFBPs) control bioavailability, activity, and distribution of insulin-like growth factor (IGF)1 and -2 through high-affinity IGFBP/IGF complexes. IGF-binding sites are found on N- and C-terminal fragments of IGFBPs, the two conserved domains of IGFBPs. The relative contributions of these domains to IGFBP/IGF complexation has been difficult to analyze, in part, because of the lack of appropriate three-dimensional structures. To analyze the effects of N- and C-terminal domain interactions, we determined several x-ray structures: first, of a ternary complex of N- and C-terminal domain fragments of IGFBP4 and IGF1 and second, of a "hybrid" ternary complex using the C-terminal domain fragment of IGFBP1 instead of IGFBP4. We also solved the binary complex of the N-terminal domains of IGFBP4 and IGF1, again to analyze C- and N-terminal domain interactions by comparison with the ternary complexes. The structures reveal the mechanisms of IGF signaling regulation via IGFBP binding. This finding supports research into the design of IGFBP variants as therapeutic IGF inhibitors for diseases of IGF disregulation. In IGFBP4, residues 1-38 form a rigid disulphide bond ladder-like structure, and the first five N-terminal residues bind to IGF and partially mask IGF residues responsible for the type 1 IGF receptor binding. A high-affinity IGF1-binding site is located in a globular structure between residues 39 and 82. Although the C-terminal domains do not form stable binary complexes with either IGF1 or the N-terminal domain of IGFBP4, in the ternary complex, the C-terminal domain contacts both and contributes to blocking of the IGF1 receptor-binding region of IGF1.

| S-EPMC1551901 | biostudies-literature

Vitamin D in Neurological Diseases.

Project description:Vitamin D may have multiple effects on the nervous system and its deficiency can represent a possible risk factor for the development of many neurological diseases. Recent studies are also trying to clarify the different effects of vitamin D supplementation over the course of progressive neurological diseases. In this narrative review, we summarise vitamin D chemistry, metabolism, mechanisms of action, and the recommended daily intake. The role of vitamin D on gene transcription and the immune response is also reviewed. Finally, we discuss the scientific evidence that links low 25-hydroxyvitamin D concentrations to the onset and progression of severe neurological diseases, such as multiple sclerosis, Parkinson's disease, Alzheimer's disease, migraine, diabetic neuropathy and amyotrophic lateral sclerosis. Completed and ongoing clinical trials on vitamin D supplementation in neurological diseases are listed.

| S-EPMC9820561 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data