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Neurodegenerative and neuromuscular disorders can manifest throughout the lifespan of an individual, from infant to elderly individuals. Axonal and synaptic degeneration are early and critical elements of nearly all human neurodegenerative diseases and neural injury, however the molecular mechanisms which regulate this process are yet to be fully elucidated. Furthermore, how the molecular mechanisms governing degeneration are impacted by the age of the individual is poorly understood. Interestingly, in mice which are under 3 weeks of age, the degeneration of axons and synapses following hypoxic or traumatic injury is significantly slower. This process, known as Wallerian degeneration (WD), is a molecularly and morphologically distinct subtype of neurodegeneration by which axons and synapses undergo distinct fragmentation and death following a range of stimuli. In this study, we first use an ex-vivo model of axon injury to confirm the significant delay in WD in neonatal mice. We apply tandem mass-tagging quantitative proteomics to profile both nerve and muscle between P12 and P24 inclusive. Application of unbiased in silico workflows to relevant protein identifications highlights a steady elevation in oxidative phosphorylation cascades corresponding to the accelerated degeneration rate. We demonstrate that inhibition of Complex I prevents the axotomy-induced rise in reactive oxygen species and protects axons following injury. Furthermore, we reveal that pharmacological activation of oxidative phosphorylation significantly accelerates degeneration at the neuromuscular junction in neonatal mice. In summary, we reveal dramatic changes in the neuromuscular proteome during post-natal maturation of the neuromuscular system, and demonstrate that endogenous dynamics in mitochondrial bioenergetics during this time window have a functional impact upon regulating the stability of the neuromuscular system.
Pubmed ID: 31176719
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Bioinformatics resource system including web server and web service for functional annotation and enrichment analyses of gene lists. Consists of comprehensive knowledgebase and set of functional analysis tools. Includes gene centered database integrating heterogeneous gene annotation resources to facilitate high throughput gene functional analysis.
View all literature mentionsA software application for such tasks as photo retouching, image composition and image authoring. It has many capabilities such as it can be used as a simple paint program, an expert quality photo retouching program, an online batch processing system, a mass production image renderer, an image format converter, etc. GIMP is expandable and extensible and designed to be augmented with plug-ins and extensions. The advanced scripting interface allows everything from the simplest task to the most complex image manipulation procedures to be easily scripted.
View all literature mentionsBioLayout Express3D is a powerful new tool for the visualization and analysis of networks derived from biological systems. Network-based approaches are becoming increasing popular for the analysis of ''omics and other high dimensional data. Networks can be produced from a wide variety of biological relationships, such as interactions between individuals, disease transmission, sequence similarity, metabolic pathways, protein interactions, pathways, regulatory cascades, gene expression, etc. BioLayout Express3D has been specifically designed for visualization, clustering and analysis of large network graphs in two- and three-dimensional space derived primarily, but not exclusively, from biological data. Sponsors: This resource is supported by BBSRC (BB / F003722 / 1) and the Wellcome Trust (GR077040RP). Keywords: Biology, Tool, Software, visualization, Analysis, Network, Biological, System, Dimentional, Data, Disease, Transmission, Sequence, Metabolic, Pathway, Protein, Interaction, Gene, Expression, Clustering, Analysis,
View all literature mentionsA horizontally and vertically structured database that pulls scientific and medical information and describes it consistently using the Ingenuity Ontology. The Knowledge Base pulls information from journals, public molecular content databases, and textbooks. Data is curated and and integrated into the Knowledge Base .
View all literature mentionsA web-based software application that enables users to analyze, integrate, and understand data derived from gene expression, microRNA, and SNP microarrays, metabolomics, proteomics, and RNA-Seq experiments, and small-scale experiments that generate gene and chemical lists. Users can search for targeted information on genes, proteins, chemicals, and drugs, and build interactive models of experimental systems. IPA allows exploration of molecular, chemical, gene, protein and miRNA interactions, creation of custom molecular pathways, and the ability to view and modify metabolic, signaling, and toxicological canonical pathways. In addition to the networks and pathways that can be created, IPA can provide multiple layering of additional information, such as drugs, disease genes, expression data, cellular functions and processes, or a researchers own genes or chemicals of interest.
View all literature mentionsA commercial antibody supplier which supplies primary and secondary antibodies, biochemicals, proteins, peptides, lysates, immunoassays and other kits.
View all literature mentionsSoftware for image processing, analysis, and editing. The software includes features such as touch capabilities, a customizable toolbar, 2D and 3D image merging, and Cloud access and options.
View all literature mentionsA software package and server used to identify and characterize proteins from primary sequence databases using mass spectrometry data. Mascot integrates peptide mass fingerprinting, sequence querying, and MS/MS ion searching in order to search for proteins in databases like SwissProt, NCBInr, EMBL EST divisions, contaminants, and cRAP. If a license is purchased, users may: search data sets that exceed the 1200 spectrum limit of the free version; set up automated, high throughput work; add and edit proteins and quantification methods; and search a preferred collection of sequence databases. The software package works with instruments from AB Sciex, Agilent, Bruker, Jeol, Shimadzu, Thermo Scientific, and Waters.
View all literature mentionsSoftware application with data analysis tools and spreadsheet templates to track and visualize data. It is used to manage and process data.
View all literature mentionsFightSMA, known legally as Andrew''s Buddies Corporation, was created to strategically accelerate the search for a treatment and cure for spinal muscular atrophy (SMA), the number-one inherited cause of infant death. The organization pursues this objective by raising awareness and funding for SMA research.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
View all literature mentionsMus musculus with name C57BL/6J from IMSR.
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