Search results: Found 4

Listing 1 - 4 of 4
Sort by
Experimental models of early exposure to alcohol: a way to unravel the neurobiology of mental retardation

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194728 Year: Pages: 104 DOI: 10.3389/978-2-88919-472-8 Language: English
Publisher: Frontiers Media SA
Subject: Pediatrics --- Psychiatry --- Medicine (General)
Added to DOAB on : 2016-03-10 08:14:33
License:

Loading...
Export citation

Choose an application

Abstract

Excessive alcohol drinking represents a major social and public health problem for several countries. Alcohol abuse during pregnancy leads to a complex syndrome referred to as fetal alcohol spectrum disorders (FASD), chiefly characterized by mental retardation. The effects of early exposure to ethanol can be reproduced in laboratory animals and this helped to answer several key questions concerning the human pathology. The interest of experimental models of FASD is twofold. First, they increase our knowledge about the dose and modality of alcohol consumption able to induce damaging effects on the developing brain. Second, experimental models of FASD can provide useful hints to elucidate the basic mechanisms leading to the intellectual disability. In fact, experimental exposure to alcohol can be carried out during discrete, often very restricted, time windows. As a consequence, FASD models, though depending on the multifaceted interference of alcohol with several molecular pathways, can provide valuable information about which specific developmental periods and brain areas are critically involved in the genesis of mental retardation. Putting together data obtained through several experimental paradigms of alcohol exposure and those deriving from other genetic and non-genetic models, one can figure out to what extent different types of mental retardation share common pathogenetic mechanisms. The present Research Topic is aimed at establishing the state of the art of the current research on experimental FASD, focusing on differences and homologies with other types of intellectual disability. The ultimate goal is to find out a common roadmap in view of future therapeutical approaches.

Molecular, Cellular and Model Organism Approaches for Understanding the Basis of Neurological Disease

Authors: ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889451739 Year: Pages: 183 DOI: 10.3389/978-2-88945-173-9 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2017-08-28 14:01:09
License:

Loading...
Export citation

Choose an application

Abstract

The advent of next-generation sequencing technologies has resulted in a remarkable increase our understanding of human and animal neurological disorders through the identification of disease causing or protective sequence variants. However, in many cases, robust disease models are required to understand how changes at the DNA, RNA or protein level affect neuronal and synaptic function, or key signalling pathways. In turn, these models may enable understanding of key disease processes and the identification of new targets for the medicines of the future. This e-book contains original research papers and reviews that highlight either the impact of next-generation sequencing in the understanding of neurological disorders, or utilise molecular, cellular, and whole-organism models to validate disease-causing or protective sequence variants.

Towards Mechanism-based Treatments for Fragile X Syndrome

Authors: ---
ISBN: 9783039215058 / 9783039215065 Year: Pages: 250 DOI: 10.3390/books978-3-03921-506-5 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:15
License:

Loading...
Export citation

Choose an application

Abstract

It has been more than 25 years since the identification of the FMR1 gene and the demonstration of the causative role of CGG-repeat expansion in the disease pathology of fragile X syndrome (FXS), but the underlying mechanisms involved in the expansion mutation and the resulting gene silencing still remain elusive. Our understanding of the pathways impacted by the loss of FMRP function has grown tremendously, and has opened new avenues for targeted treatments for FXS. However, the failure of recent clinical trials that were based on successful preclinical studies using the Fmr1 knockout mouse model has forced the scientific community to revisit clinical trial design and identify objective outcome measures. There has also been a renewed interest in restoring FMR1 gene expression as a possible treatment approach for FXS. This special issue of Brain Sciences highlights the progress that has been made towards understanding the disease mechanisms and how this has informed the development of treatment strategies that are being explored for FXS.

Keywords

fragile X syndrome --- clinical trials --- targeted treatments --- drug development --- fragile X syndrome --- clinical trials --- treatment development --- best practices --- fragile X syndrome --- newborn screening --- early identification --- fragile X syndrome --- X chromosome --- females --- FMR1 --- anxiety --- avoidance --- cognition --- behavior --- brain --- Fragile X --- FMRP --- Fxr2 --- Fmr1 --- fragile X syndrome --- executive function --- working memory --- set-shifting --- cognitive flexibility --- inhibitory control --- attention --- planning --- processing speed --- Fragile X syndrome 1 --- Fragile X-associated Tremor/Ataxia Syndrome 2 --- CRISPR 3 --- Trinucleotide Repeat 4 --- Gene editing --- fragile X syndrome --- FMR1 gene --- voice of the person --- voice of the patient --- characteristics that have the greatest impact --- developmental disorders --- fragile X syndrome --- language development --- automated vocal analysis --- adeno-associated virus --- autism spectrum disorders --- cerebral spinal fluid --- fragile X mental retardation protein --- neurodevelopmental disorders --- viral vector --- fragile X syndrome --- gene reactivation --- RNA:DNA hybrid --- FMRP --- histone methylation --- DNA methylation --- FMR1 --- PRC2 --- fragile X syndrome --- unstable repeat diseases --- epigenetic gene silencing --- DNA methylation --- repeat instability --- pluripotent stem cells --- CGG Repeat Expansion Disease --- DNA instability --- expansion --- contraction --- mismatch repair (MMR) --- base excision repair (BER) --- transcription coupled repair (TCR) --- double-strand break repair (DSBR) --- Non-homologous end-joining (NHEJ) --- mosaicism --- protein synthesis --- Fragile X Syndrome --- biomarker --- iPSC --- fibroblast --- lymphoblast --- fragile X syndrome --- molecular biomarkers --- FMR1 --- FMRP --- intellectual disability --- Fmr1 KO mouse --- ASD --- n/a

Polyamine Metabolism in Disease and Polyamine-Targeted Therapies

Author:
ISBN: 9783039211524 / 9783039211531 Year: Pages: 240 DOI: 10.3390/books978-3-03921-153-1 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Science (General) --- Biology
Added to DOAB on : 2019-12-09 11:49:15
License:

Loading...
Export citation

Choose an application

Abstract

Polyamines are ubiquitous polycations essential for all cellular life. The most common polyamines in eukaryotes, spermine, spermidine, and putrescine, exist in millimolar intracellular concentrations that are tightly regulated through biosynthesis, catabolism, and transport. Polyamines interact with, and regulate, negatively charged macromolecules, including nucleic acids, proteins, and ion channels. Accordingly, alterations in polyamine metabolism affect cellular proliferation and survival through changes in gene expression and transcription, translation, autophagy, oxidative stress, and apoptosis. Dysregulation of these multifaceted polyamine functions contribute to multiple disease processes, thus their metabolism and function have been targeted for preventive or therapeutic intervention. The correlation between elevated polyamine levels and cancer is well established, and ornithine decarboxylase, the rate-limiting biosynthetic enzyme in the production of putrescine, is a bona fide transcriptional target of the Myc oncogene. Furthermore, induced polyamine catabolism contributes to carcinogenesis that is associated with certain forms of chronic infection and/or inflammation through the production of reactive oxygen species. These and other characteristics specific to cancer cells have led to the development of polyamine-based agents and inhibitors aimed at exploiting the polyamine metabolic pathway for chemotherapeutic and chemopreventive benefit. In addition to cancer, polyamines are involved in the pathologies of neurodegenerative diseases including Alzheimer’s and Parkinson’s, parasitic and infectious diseases, wound healing, ischemia/reperfusion injuries, and certain age-related conditions, as polyamines are known to decrease with age. As in cancer, polyamine-based therapies for these conditions are an area of active investigation. With recent advances in immunotherapy, interest has increased regarding polyamine-associated modulation of immune responses, as well as potential immunoregulation of polyamine metabolism, the results of which could have relevance to multiple disease processes. The goal of this Special Issue of Medical Sciences is to present the most recent advances in polyamine research as it relates to health, disease, and/or therapy.

Keywords

polyamine transport inhibitor --- Drosophila imaginal discs --- difluoromethylorthinine --- DFMO --- polyamine --- cancer --- metabolism --- difluoromethylornithine --- polyamine transport inhibitor --- pancreatic ductal adenocarcinoma --- curcumin --- diferuloylmethane --- ornithine decarboxylase --- polyamine --- NF-?B --- chemoprevention --- carcinogenesis --- polyphenol --- ornithine decarboxylase --- polyamines --- untranslated region --- polyamines --- ?-difluoromethylornithine --- polyamine transport system --- melanoma --- mutant BRAF --- spermine --- spermidine --- putrescine --- polyamine metabolism --- mast cells --- eosinophils --- neutrophils --- M2 macrophages --- airway smooth muscle cells --- Streptococcus pneumoniae --- polyamines --- pneumococcal pneumonia --- proteomics --- capsule --- complementation --- metabolism --- cadaverine --- polyamines --- ornithine decarboxylase --- difluoromethylornithine --- eflornithine --- DFMO --- African sleeping sickness --- hirsutism --- colorectal cancer --- neuroblastoma --- aging --- atrophy --- autophagy --- oxidative stress --- polyamines --- skeletal muscle --- spermidine --- spermine oxidase --- transgenic mouse --- immunity --- T-lymphocytes --- B-lymphocytes --- tumor immunity --- metabolism --- epigenetics --- autoimmunity --- polyamines --- ornithine decarboxylase --- polyamine analogs --- spermidine/spermine N1-acetyl transferase --- spermine oxidase --- bis(ethyl)polyamine analogs --- breast cancer --- MCF-7 cells --- transgenic mice --- polyamines --- MYC --- protein synthesis in cancer --- neuroblastoma --- protein expression --- antizyme 1 --- ornithine decarboxylase --- CRISPR --- human embryonic kidney 293 (HEK293) --- cell differentiation --- DFMO --- ornithine decarboxylase --- osteosarcoma --- polyamines --- polyamines --- polyamine metabolism --- antizyme --- antizyme inhibitors --- ornithine decarboxylase --- Snyder-Robinson Syndrome --- spermine synthase --- X-linked intellectual disability --- polyamine transport --- spermidine --- spermine --- transglutaminase

Listing 1 - 4 of 4
Sort by
Narrow your search