Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Animal Models of CMT2A: State-of-art and Therapeutic Implications.

ABSTRACT: Charcot-Marie-Tooth disease type 2A (CMT2A), arising from mitofusin 2 (MFN2) gene mutations, is the most common inherited axonal neuropathy affecting motor and sensory neurons. The cellular and molecular mechanisms by which MFN2 mutations determine neuronal degeneration are largely unclear. No effective treatment exists for CMT2A, which has a high degree of genetic/phenotypic heterogeneity. The identification of mutations in MFN2 has allowed the generation of diverse transgenic animal models, but to date, their ability to recapitulate the CMT2A phenotype is limited, precluding elucidation of its pathogenesis and discovery of therapeutic strategies. This review will critically present recent progress in in vivo CMT2A disease modeling, discoveries, drawbacks and limitations, current challenges, and key reflections to advance the field towards developing effective therapies for these patients.

SUBMITTER: De Gioia R

PROVIDER: S-EPMC7541381 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Animal Models of CMT2A: State-of-art and Therapeutic Implications.

De Gioia Roberta R Citterio Gaia G Abati Elena E Nizzardo Monica M Bresolin Nereo N Comi Giacomo Pietro GP Corti Stefania S Rizzo Federica F

Molecular neurobiology 20200827 12

Charcot-Marie-Tooth disease type 2A (CMT2A), arising from mitofusin 2 (MFN2) gene mutations, is the most common inherited axonal neuropathy affecting motor and sensory neurons. The cellular and molecular mechanisms by which MFN2 mutations determine neuronal degeneration are largely unclear. No effective treatment exists for CMT2A, which has a high degree of genetic/phenotypic heterogeneity. The identification of mutations in MFN2 has allowed the generation of diverse transgenic animal models, bu ...[more]

PMID: 32856204

Similar Datasets

Animal models of necrotizing enterocolitis: review of the literature and state of the art.

Project description:Necrotizing enterocolitis (NEC) remains the leading cause of gastrointestinal surgical emergency in preterm neonates. Over the last five decades, a variety of experimental models have been developed to study the pathophysiology of this disease and to test the effectiveness of novel therapeutic strategies. Experimental NEC is mainly modeled in neonatal rats, mice and piglets. In this review, we focus on these experimental models and discuss the major advantages and disadvantages of each. We also briefly discuss other models that are not as widely used but have contributed to our current knowledge of NEC.

| S-EPMC6604570 | biostudies-literature

Therapeutic siRNA: state of the art.

Project description:RNA interference (RNAi) is an ancient biological mechanism used to defend against external invasion. It theoretically can silence any disease-related genes in a sequence-specific manner, making small interfering RNA (siRNA) a promising therapeutic modality. After a two-decade journey from its discovery, two approvals of siRNA therapeutics, ONPATTRO® (patisiran) and GIVLAARI™ (givosiran), have been achieved by Alnylam Pharmaceuticals. Reviewing the long-term pharmaceutical history of human beings, siRNA therapy currently has set up an extraordinary milestone, as it has already changed and will continue to change the treatment and management of human diseases. It can be administered quarterly, even twice-yearly, to achieve therapeutic effects, which is not the case for small molecules and antibodies. The drug development process was extremely hard, aiming to surmount complex obstacles, such as how to efficiently and safely deliver siRNAs to desired tissues and cells and how to enhance the performance of siRNAs with respect to their activity, stability, specificity and potential off-target effects. In this review, the evolution of siRNA chemical modifications and their biomedical performance are comprehensively reviewed. All clinically explored and commercialized siRNA delivery platforms, including the GalNAc (N-acetylgalactosamine)-siRNA conjugate, and their fundamental design principles are thoroughly discussed. The latest progress in siRNA therapeutic development is also summarized. This review provides a comprehensive view and roadmap for general readers working in the field.

| S-EPMC7305320 | biostudies-literature

Adrenocortical Carcinoma: Current Therapeutic State-of-the-Art.

Project description:Adrenocortical carcinoma (ACC) is a rare, aggressive malignancy that generally conveys a poor prognosis. Currently, surgical resection is considered the lone curative treatment modality. In addition, the low prevalence of ACC has limited effective clinical trial design to develop evidence-based approaches to ACC therapy. The proper role of radio- and chemotherapy treatment for ACC is still being defined. Similarly, the molecular pathogenesis of ACC remains to be fully characterized. Despite these challenges, progress has been made in several areas. After years of refinement, an internationally accepted staging system has been defined. International collaborations have facilitated increasingly robust clinical trials, especially regarding agent choice and patient selection for chemotherapeutics. Genetic array data and molecular profiling have identified new potential targets for rational drug design as well as potential tumor markers and predictors of therapeutic response. However, these advances have not yet been translated into a large outcomes benefit for ACC patients. In this paper, we summarize established therapy for ACC and highlight recent findings in the field that are impacting clinical practice.

| S-EPMC3483813 | biostudies-literature

Study of lncRNAs in Pediatric Neurological Diseases: Methods, Analysis of the State-of-Art and Possible Therapeutic Implications.

Project description:Long non-coding RNAs (lncRNAs) have emerged as crucial regulators in various cellular processes, and their roles in pediatric neurological diseases are increasingly being explored. This review provides an overview of lncRNA implications in the central nervous system, both in its physiological state and when a pathological condition is present. We describe the role of lncRNAs in neural development, highlighting their significance in processes such as neural stem cell proliferation, differentiation, and synaptogenesis. Dysregulation of specific lncRNAs is associated with multiple pediatric neurological diseases, such as neurodevelopmental or neurodegenerative disorders and brain tumors. The collected evidence indicates that there is a need for further research to uncover the full spectrum of lncRNA involvement in pediatric neurological diseases and brain tumors. While challenges exist, ongoing advancements in technology and our understanding of lncRNA biology offer hope for future breakthroughs in the field of pediatric neurology, leveraging lncRNAs as potential therapeutic targets and biomarkers.

| S-EPMC10675345 | biostudies-literature

Therapeutic siRNA: State-of-the-Art and Future Perspectives.

Project description:The highly specific induction of RNA interference-mediated gene knockdown, based on the direct application of small interfering RNAs (siRNAs), opens novel avenues towards innovative therapies. Two decades after the discovery of the RNA interference mechanism, the first siRNA drugs received approval for clinical use by the US Food and Drug Administration and the European Medicines Agency between 2018 and 2022. These are mainly based on an siRNA conjugation with a targeting moiety for liver hepatocytes, N-acetylgalactosamine, and cover the treatment of acute hepatic porphyria, transthyretin-mediated amyloidosis, hypercholesterolemia, and primary hyperoxaluria type 1. Still, the development of siRNA therapeutics faces several challenges and issues, including the definition of optimal siRNAs in terms of target, sequence, and chemical modifications, siRNA delivery to its intended site of action, and the absence of unspecific off-target effects. Further siRNA drugs are in clinical studies, based on different delivery systems and covering a wide range of different pathologies including metabolic diseases, hematology, infectious diseases, oncology, ocular diseases, and others. This article reviews the knowledge on siRNA design and chemical modification, as well as issues related to siRNA delivery that may be addressed using different delivery systems. Details on the mode of action and clinical status of the various siRNA therapeutics are provided, before giving an outlook on issues regarding the future of siRNA drugs and on their potential as one emerging standard modality in pharmacotherapy. Notably, this may also cover otherwise un-druggable diseases, the definition of non-coding RNAs as targets, and novel concepts of personalized and combination treatment regimens.

| S-EPMC9396607 | biostudies-literature

Mouse models of ciliopathies: the state of the art.

Project description:The ciliopathies are an apparently disparate group of human diseases that all result from defects in the formation and/or function of cilia. They include disorders such as Meckel-Grüber syndrome (MKS), Joubert syndrome (JBTS), Bardet-Biedl syndrome (BBS) and Alström syndrome (ALS). Reflecting the manifold requirements for cilia in signalling, sensation and motility, different ciliopathies exhibit common elements. The mouse has been used widely as a model organism for the study of ciliopathies. Although many mutant alleles have proved lethal, continued investigations have led to the development of better models. Here, we review current mouse models of a core set of ciliopathies, their utility and future prospects.

| S-EPMC3339824 | biostudies-literature

Effects of dioxins on animal spermatogenesis: A state-of-the-art review.

Project description:The male reproductive system is especially affected by dioxins, a group of persistent environmental pollutants, resulting in irreversible abnormalities including effects on sexual function and fertility in adult males and possibly on the development of male offspring. The reproductive toxicity caused by dioxins is mostly mediated by an aryl hydrocarbon receptor (AhR). In animals, spermatogenesis is a highly sensitive and dynamic process that includes proliferation and maturation of germ cells. Spermatogenesis is subject to multiple endogenous and exogenous regulatory factors, including a wide range of environmental toxicants such as dioxins. This review discusses the toxicological effects of dioxins on spermatogenesis and their relevance to male infertility. After a detailed categorization of the environmental contaminants affecting the spermatogenesis, the exposure pathways and bioavailability of dioxins in animals was briefly reviewed. The effects of dioxins on spermatogenesis are then outlined in detail. The endocrine-disrupting effects of dioxins in animals and humans are discussed with a particular focus on their effects on the expression of spermatogenesis-related genes. Finally, the impacts of dioxins on the ratio of X and Y chromosomes, the status of serum sex hormones, the quality and fertility of sperm, and the transgenerational effects of dioxins on male reproduction are reviewed.

| S-EPMC9634422 | biostudies-literature

Zoonotic RVA: State of the Art and Distribution in the Animal World.

Project description:Rotavirus species A (RVA) is a pathogen mainly affecting children under five years old and young animals. The infection produces acute diarrhea in its hosts and, in intensively reared livestock animals, can cause severe economic losses. In this study, we analyzed all RVA genomic constellations described in animal hosts. This review included animal RVA strains in humans. We compiled detection methods, hosts, genotypes and complete genomes. RVA was described in 86 animal species, with 52% (45/86) described by serology, microscopy or the hybridization method; however, strain sequences were not described. All of these reports were carried out between 1980 and 1990. In 48% (41/86) of them, 9251 strain sequences were reported, with 28% being porcine, 27% bovine, 12% equine and 33% from several other animal species. Genomic constellations were performed in 80% (32/40) of hosts. Typical constellation patterns were observed in groups such as birds, domestic animals and artiodactyls. The analysis of the constellations showed RVA's capacity to infect a broad range of species, because there are RVA genotypes (even entire constellations) from animal species which were described in other studies. This suggests that this virus could generate highly virulent variants through gene reassortments and that these strains could be transmitted to humans as a zoonotic disease, making future surveillance necessary for the prevention of future outbreaks.

| S-EPMC9694813 | biostudies-literature

Vitiligo, from Pathogenesis to Therapeutic Advances: State of the Art.

Project description:Vitiligo is an acquired hypopigmentation of the skin due to a progressive selective loss of melanocytes; it has a prevalence of 1-2% and appears as rounded, well-demarcated white macules. The etiopathology of the disease has not been well defined, but multiple factors contribute to melanocyte loss: metabolic abnormalities, oxidative stress, inflammation, and autoimmunity. Therefore, a convergence theory was proposed that combines all existing theories into a comprehensive one in which several mechanisms contribute to the reduction of melanocyte viability. In addition, increasingly in-depth knowledge about the disease's pathogenetic processes has enabled the development of increasingly targeted therapeutic strategies with high efficacy and fewer side effects. The aim of this paper is, by conducting a narrative review of the literature, to analyze the pathogenesis of vitiligo and the most recent treatments available for this condition.

| S-EPMC10003418 | biostudies-literature

Cancer screening simulation models: a state of the art review.

Project description:BackgroundNowadays, various simulation approaches for evaluation and decision making in cancer screening can be found in the literature. This paper presents an overview of approaches used to assess screening programs for breast, lung, colorectal, prostate, and cervical cancers. Our main objectives are to describe methodological approaches and trends for different cancer sites and study populations, and to evaluate quality of cancer screening simulation studies.MethodsA systematic literature search was performed in Medline, Web of Science, and Scopus databases. The search time frame was limited to 1999-2018 and 7101 studies were found. Of them, 621 studies met inclusion criteria, and 587 full-texts were retrieved, with 300 of the studies chosen for analysis. Finally, 263 full texts were used in the analysis (37 were excluded during the analysis). A descriptive and trend analysis of models was performed using a checklist created for the study.ResultsCurrently, the most common methodological approaches in modeling cancer screening were individual-level Markov models (34% of the publications) and cohort-level Markov models (41%). The most commonly evaluated cancer types were breast (25%) and colorectal (24%) cancer. Studies on cervical cancer evaluated screening and vaccination (18%) or screening only (13%). Most studies have been conducted for North American (42%) and European (39%) populations. The number of studies with high quality scores increased over time.ConclusionsOur findings suggest that future directions for cancer screening modelling include individual-level Markov models complemented by screening trial data, and further effort in model validation and data openness.

| S-EPMC8690438 | 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