Springer protocols feed by Neuroscience 
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This is an RSS file. You can use it to subscribe to this data in your favourite RSS reader or to display this data on your own website or blog.Gene Therapy Approaches Using Reproducible and Fully Penetrant Lentivirus-Mediated Endogenous Glioma Models
Animal models have proven invaluable for progress toward greater understanding of the etiology, pathogenesis, and genetics of a wide range of human diseases. The development of relevant brain tumor animal models is a critical resource for building our understanding of cancers that arise within the brain and for the development of novel therapies. The central role of these models is particularly apparent for gliomas, which are common and devastating primary brain tumors. Effective models accurately demonstrate pathological features and behavior that are analogous to the human disease. Models aim to develop tumors with high ...
Source: Springer protocols feed by Neuroscience - January 10, 2015 Category: Neuroscience Source Type: news
Adeno-Associated Vectors for Gene Delivery to the Nervous System
Gene therapy approaches based on adeno-associated viral vector (AAV) systems offer many unique advantages for nervous system applications. These vectors are opening up new approaches for the treatment of neurodegenerative diseases. AAV can efficiently deliver genes to postmitotic neuronal cell types offering long-term expression, can be generated in high titers, and are associated with only minimal immunological complications. Numerous animal studies have demonstrated the efficiency of these vectors both at preclinical and clinical development stages. The current chapter will describe the basic features of AAV vectors, lis...
Source: Springer protocols feed by Neuroscience - January 10, 2015 Category: Neuroscience Source Type: news
Lentiviral Vectors for Gene Delivery to the Nervous System
The efficient management and development of therapeutic strategies for disorders of the nervous system still remains a major medical challenge. Gene therapy for the nervous system diseases is particularly challenging due to the post-mitotic nature of neuronal cells and the restricted accessibility of the brain itself. Viral vectors based on lentiviruses are particularly attractive vehicles, routinely used in developing gene-based therapies to treat neurological diseases. Due to their unique properties, which allow them to transduce most nervous system cell types, maintaining strong, and long-term transgene expression, they...
Source: Springer protocols feed by Neuroscience - January 10, 2015 Category: Neuroscience Source Type: news
Gene Delivery and Gene Therapy for Alzheimer’s Disease
Adeno-associated virus (AAV) is the most widely used vector for gene therapy clinical trials focused on neurodegeneration. Not only can it safely and efficiently confer long-term expression in a variety of cell types, but innovations including hybrid serotypes, rationally designed capsids, split vectors, specific promoter/enhancer additions, and convection-enhanced delivery have greatly progressed the field of AAV research for neurodegenerative disease. Indeed, these developments, which enable increased specificity, efficiency, and spread of gene transfer as well as ease of administration to the CNS, have pushed AAV forwar...
Source: Springer protocols feed by Neuroscience - January 10, 2015 Category: Neuroscience Source Type: news
Gene Therapy for Parkinson’s Disease: AAV5-Mediated Delivery of Glial Cell Line-Derived Neurotrophic Factor (GDNF)
Parkinson’s disease (PD) is characterized by neurodegeneration of the dopaminergic neurons. Glial cell line-derived neurotrophic factor (GDNF) has been identified as possible therapeutic molecule for the treatment of neurodegenerative diseases in several different animal models. Delivery of the GDNF has been proven to be very efficient using recombinant AAV vectors. AAV2 has been widely used for the delivery of transgenes to the brain and has even led to a clinical trial for the treatment of PD. A serotype that is known for highly effective delivery of its transgene to the brain is AAV serotype 5. At uniQure, we have...
Source: Springer protocols feed by Neuroscience - January 10, 2015 Category: Neuroscience Source Type: news
Gene Therapy for Huntington’s Disease
Huntington’s disease (HD) is an inherited autosomal dominant neurodegenerative disease characterized by loss of motor control, cognitive decline, and psychiatric manifestations. The underlying genetic cause of HD is a mutation in the huntingtin gene resulting in an expanded polyglutamine tract in huntingtin protein that confers a toxic gain of function. Abnormal intranuclear protein inclusions and the progressive degeneration of medium spiny neurons in the striatum as well as other brain areas at later stages are key neuropathological features of the disease. Gene therapy is an attractive therapeutic option for HD. T...
Source: Springer protocols feed by Neuroscience - January 10, 2015 Category: Neuroscience Source Type: news
Gene Therapy Approaches to Promoting Axonal Regeneration After Spinal Cord Injury
Traumatic spinal cord injury is a devastating medical condition that still lacks any effective treatment. Studies on the pathological processes of spinal cord injury and neural repair indicate that the two main obstacles that prevent successful axonal regeneration and functional recovery are the weak intrinsic regenerative capacity of the neurons and the presence of several types of inhibitory molecules in the central nervous system (CNS). Various strategies have been derived and tested to elevate the regenerative status of injured neurons in the CNS or block the inhibitory molecules. Gene therapy approaches have been view...
Source: Springer protocols feed by Neuroscience - January 10, 2015 Category: Neuroscience Source Type: news
Gene Delivery to Neurons of the Dorsal Root Ganglia Using Adeno-Associated Viral Vectors
We describe detailed procedures to perform direct injections into specific DRG and delivery via the intrathecal space to transduce the lumbar DRG. Finally, we discuss the specific advantages and disadvantages of these two methods of delivery. The main advantages of direct injection are that high transduction rates can be achieved in specific ganglia (L4/L5) with low amounts (μl) of a viral vector stock; however, the procedure is complex, invasive, and time-consuming. Intrathecal injection has the advantage of being a fast and simple method to transduce multiple DRG bilaterally, and involves no surgical manipulation of t...
Source: Springer protocols feed by Neuroscience - January 10, 2015 Category: Neuroscience Source Type: news
Targeted Gene Therapy for Ischemic Stroke
Exogenous delivery of angiogenic and neuroprotective genes has been shown to enhance innate compensatory responses after ischemic injury. However, there are certain barriers in translating gene-based therapy to the clinical setting. For example, systemic delivery of genes into the brain is prevented by the blood–brain barrier (BBB); intraventricular delivery results in nonspecific distribution and gene expression; and stereotactic injection of vectors into the ischemic penumbra requires an invasive procedure that can cause additional damage. This chapter describes an adeno-associated viral (AAV) vector with two prima...
Source: Springer protocols feed by Neuroscience - January 10, 2015 Category: Neuroscience Source Type: news
Adeno-Associated Viral Gene Therapy for Retinal Disorders
Gene therapy is ideally suited to the treatment of inherited retinal degenerations in order to prevent blindness. The target area of the outer retina is small and relatively immune privileged, which facilitates the delivery of small volumes of vector without generating significant immune reactions. Moreover, most of the currently untreatable forms of blindness have a genetic component, either monogenic such as in retinitis pigmentosa or as a result of several genes interacting along a common pathway, such as age-related macular degeneration, the commonest cause of legal blindness in the developed world. The self-contained ...
Source: Springer protocols feed by Neuroscience - January 10, 2015 Category: Neuroscience Source Type: news
Gene Expression-Based Approaches to Understanding Huntington’s Disease and New Tools for the Interpretation of Expression Datasets
Expression profiling has become a well-established and widely utilized approach to generate and support hypotheses regarding biological processes. Etiopathologic mechanisms of Huntingtin toxicity include transcriptional dysregulation [reviewed in Luthi-Carter (Drug Dis Today Dis Mech 4:111–119, 2007)], and a strikingly characteristic set of HD-related changes in gene expression have been informative in assessing model systems and underlying pathological (and compensatory) mechanisms [reviewed in Seredenina and Luthi-Carter (Neurobiol Dis 45:83–98, 2012)]. (Source: Springer protocols feed by Neuroscience)
Source: Springer protocols feed by Neuroscience - January 1, 2015 Category: Neuroscience Source Type: news
An Overview of Methods Used in Neurogenomics and Their Applications
This chapter is an introduction to and an overview of neurogenomics—an analysis of genes in the nervous system and their application for diagnosis as well as potential therapeutics of disorders of the nervous system. The most important technologies are those for sequencing. Traditional as well as new techniques are described briefly including next-generation sequencing. Important applications include discovery of genomic biomarkers, brain mapping as well as connectomics, molecular diagnostics, drug discovery, and potential new therapeutics for neurologic disorders. Knowledge of the genes relevant to the nervous syste...
Source: Springer protocols feed by Neuroscience - January 1, 2015 Category: Neuroscience Source Type: news
Location Analysis and Expression Profiling Using Next-Generation Sequencing for Research in Neurodegenerative Diseases
Neurodegenerative diseases carry a huge burden in terms of human suffering and economic cost. In spite of advances in the field of neurology, there is still no effective cure. A combination of novel genomic approaches and techniques such as chromatin immunoprecipitation sequencing (ChIP-seq) and RNA-seq that enable high-quality data could provide better understanding of transcriptional and epigenetic signatures useful for both biomarker development and drug discovery in neurodegenerative diseases. This chapter provides detailed protocols of the different steps required to generate a successful ChIP-seq and RNA-seq library....
Source: Springer protocols feed by Neuroscience - January 1, 2015 Category: Neuroscience Source Type: news
RNA Sequencing from Laser Capture Microdissected Brain Tissue to Study Normal Aging and Alzheimer’s Disease
The next-generation sequencing (NGS) of RNA, or RNA-Seq, has significantly changed the way that the transcriptional content of a biological sample is investigated. RNA-Seq is a major advance for the field due to its largely unbiased and digital nature, its ability to empower RNA splice form construction at a genomic level, and its improved dynamic range when compared to a microarray technology. Investigating the healthy or diseased brain presents unique problems from the standpoint of transcriptional analysis as each cell type, and perhaps even each individual cell, is in a unique state of transcription. The organ is a com...
Source: Springer protocols feed by Neuroscience - January 1, 2015 Category: Neuroscience Source Type: news
Targeted Re-sequencing in Psychiatric Disorders
The method presented here enables researchers to sequence a target region in the genome in a large number of subjects at comparatively low cost. The method relies heavily on modern massively parallel sequencing (MPS) technologies, and the costs and workload for DNA sample preparation are major factors in targeted re-sequencing studies involving many individual samples. In order to reduce costs during sample preparation, we propose to sequence pools of subjects rather than individual subjects. Thus, our approach is divided into four subparts: (1) non-barcoded sample pooling, (2) enrichment of the target region, (3) sequenci...
Source: Springer protocols feed by Neuroscience - January 1, 2015 Category: Neuroscience Source Type: news
