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Gene Silencing and Editing Strategies for Neurodegenerative Diseases

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455515 Year: Pages: 115 DOI: 10.3389/978-2-88945-551-5 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Neurology
Added to DOAB on : 2019-01-23 14:53:42
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Abstract

Neurodegenerative diseases (NDs) are a heterogeneous group of disorders affecting the central nervous system. Despite significant differences in their causes, neuropathological abnormalities, and clinical outcomes, some similarities can be found among them, as for example: 1) frequent aggregation and deposition of misfolded proteins, 2) common molecular mechanisms leading to neurodegeneration, and 3) certain overlap in symptoms and clinical features. To date, there is no cure that could stop or delay the progression of these diseases. The advent of advanced gene therapy techniques such as gene silencing and gene editing opened a new avenue for the development of therapeutic strategies for NDs.The discovery of the RNA interference (RNAi) mechanism, in 1998, by Andrew Fire and Craig Mello allowed an important boost to the gene therapy field, providing a potential therapeutic strategy to treat inherited dominant genetic disorders. The use of small RNA sequences to control the expression of disease-causing genes rapidly implemented in the preclinical studies for different diseases. In the field of NDs, several successful studies using this technology proved its potential as a therapeutic option. However, issues like the type of delivery system (non-viral versus viral) or the potential toxicity of the small RNA molecules, made the translation of gene silencing therapeutics to human application very slow and difficult.Recently, a new hope in the gene therapy field emerged with the development of gene editing techniques like TALENs or CRISPR/Cas9 systems. The opportunity of editing or deleting gene sequences drove the scientific community euphoric, with an enormous increase in the number of published studies using this type of techniques. Recently, the first clinical trial using one of these systems was approved in China. For NDs, gene-editing technology also represents an important therapeutic option, and the first preclinical studies are now being published, showing the potential accomplishment for this technology.

The Epithelial-to-Mesenchymal Transition (EMT) in Cancer

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ISBN: 9783038427933 9783038427940 Year: Pages: VI, 254 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Biology
Added to DOAB on : 2018-04-27 16:09:54
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The epithelial-to-mesenchymal transition (EMT) is a highly dynamic process with multiple transitional states, by which epithelial cells can convert into a mesenchymal phenotype. This process involves loss of cellular adhesion and cellular polarity, and an improvement in migratory and invasive properties. It occurs during normal embryonic development, tissue regeneration, organ fibrosis, and wound healing. It is also involved in tumor progression with metastatic expansion, and plays a major role in resistance to cancer treatment. In cancers, EMT inducers are hypoxia, cytokines and growth factors secreted by the tumor microenvironment, stroma crosstalk, metabolic changes, innate and adaptive immune responses, and treatment with antitumor drugs. Switch in gene expression from epithelial to mesenchymal phenotype is triggered by complex regulatory networks involving transcriptional control, non-coding RNAs, chromatin remodeling and epigenetic modifications, alternative splicing, post-translational regulation, protein stability and subcellular localization. Reversion of EMT, the mesenchymal-to-epithelial transition (MET), affects circulating cancer cells when they reach a desirable metastatic niche to develop secondary tumors. More knowledge and control of EMT to MET is necessary and will be beneficial for patients for cancer treatment. This current Special Issue entitled “Epithelial to Mesenchymal Transition in Cancer” will address these questions.

Representation in the Brain

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889455966 Year: Pages: 147 DOI: 10.3389/978-2-88945-596-6 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Psychology
Added to DOAB on : 2019-01-23 14:53:43
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This eBook contains ten articles on the topic of representation of abstract concepts, both simple and complex, at the neural level in the brain. Seven of the articles directly address the main competing theories of mental representation – localist and distributed. Four of these articles argue – either on a theoretical basis or with neurophysiological evidence – that abstract concepts, simple or complex, exist (have to exist) at either the single cell level or in an exclusive neural cell assembly. There are three other papers that argue for sparse distributed representation (population coding) of abstract concepts. There are two other papers that discuss neural implementation of symbolic models. The remaining paper deals with learning of motor skills from imagery versus actual execution. A summary of these papers is provided in the Editorial.

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