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Synthetic PreImplantation Factor (sPIF) induces posttranslational protein modification and reverses paralysis in EAE mice.

Soren Hayrabedyan | Reut Shainer | Zhanna Yekhtin | Lola Weiss | Osnat Almogi-Hazan | Reuven Or | Charles L Farnsworth | Scott Newsome | Krassimira Todorova | Michael J Paidas | Chaya Brodie | Eytan R Barnea | Martin Mueller
Scientific reports | 2019

An autoimmune response against myelin protein is considered one of the key pathogenic processes that initiates multiple sclerosis (MS). The currently available MS disease modifying therapies have demonstrated to reduce the frequency of inflammatory attacks. However, they appear limited in preventing disease progression and neurodegeneration. Hence, novel therapeutic approaches targeting both inflammation and neuroregeneration are urgently needed. A new pregnancy derived synthetic peptide, synthetic PreImplantation Factor (sPIF), crosses the blood-brain barrier and prevents neuro-inflammation. We report that sPIF reduces paralysis and de-myelination of the brain in a clinically-relevant experimental autoimmune encephalomyelitis mice model. These effects, at least in part, are due to post-translational modifications, which involve cyclic AMP dependent protein kinase (PKA), calcium-dependent protein kinase (PKC), and immune regulation. In terms of potential MS treatment, sPIF was successfully tested in neurodegenerative animal models of perinatal brain injury and experimental autoimmune encephalitis. Importantly, sPIF received a FDA Fast Track Approval for first in human trial in autommuninty (completed).

Pubmed ID: 31578341

Associated grants

  • Agency: NCATS NIH HHS, United States
    Id: UL1 TR001863

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.


PhosphoSitePlus: Protein Modification Site (tool)

RRID:SCR_001837

A freely accessible on-line systems biology resource devoted to all aspects of protein modification, as well as other post-translational modifications. It provides valuable and unique tools for both cell biologists and mass spectroscopists. PhosphoSite is a human- and mouse-centric database. It includes features such as: viewing the locations of modified residues on molecular models; browsing and searching MS2 records by disease, tissue, and cell line; submitting lists of peptides to identify previously reported genes; searching by sub-cellular localization, treatment, tissues, cell types, cell lines and diseases, and protein types and protein domains; searching for experimentally-verified kinase substrates and viewing preferred substrate motifs; and viewing MS2 spectra for peptides and sites not previously published.

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PANTHER (tool)

RRID:SCR_004869

System that classifies genes by their functions, using published scientific experimental evidence and evolutionary relationships to predict function even in absence of direct experimental evidence. Orthologs view is curated orthology relationships between genes for human, mouse, rat, fish, worm, and fly.

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Promega (tool)

RRID:SCR_006724

An Antibody supplier

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EGAN: Exploratory Gene Association Networks (tool)

RRID:SCR_008856

Exploratory Gene Association Networks (EGAN) is a software tool that allows a bench biologist to visualize and interpret the results of high-throughput exploratory assays in an interactive hypergraph of genes, relationships (protein-protein interactions, literature co-occurrence, etc.) and meta-data (annotation, signaling pathways, etc.). EGAN provides comprehensive, automated calculation of meta-data coincidence (over-representation, enrichment) for user- and assay-defined gene lists, and provides direct links to web resources and literature (NCBI Entrez Gene, PubMed, KEGG, Gene Ontology, iHOP, Google, etc.). EGAN functions as a module for exploratory investigation of analysis results from multiple high-throughput assay technologies, including but not limited to: * Transcriptomics via expression microarrays or RNA-Seq * Genomics via SNP GWAS or array CGH * Proteomics via MS/MS peptide identifications * Epigenomics via DNA methylation, ChIP-on-Chip or ChIP-Seq * In-silico analysis of sequences or literature EGAN has been built using Cytoscape libraries for graph visualization and layout, and is comparable to DAVID, GSEA, Ingenuity IPA and Ariadne Pathway Studio. There are pre-collated EGAN networks available for human (Homo sapiens), mouse (Mus musculus), rat (Rattus norvegicus), chicken (Gallus gallus), zebrafish (Danio rerio), fruit fly (Drosophila melanogaster), nematode (Caenorhabditis elegans), mouse-ear cress (Arabidopsis thaliana), rice (Oryza sativa) and brewer's yeast (Saccharomyces cerevisiae). There is now an EGAN module available for GenePattern (human-only). Platform: Windows compatible, Mac OS X compatible, Linux compatible

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Sigma-Aldrich (tool)

RRID:SCR_008988

American chemical, life science and biotechnology company owned by Merck KGaA. Merger of Sigma Chemical Company and Aldrich Chemical Company. Provides organic and inorganic chemicals, building blocks, reagents, advanced materials and stable isotopes for chemical synthesis, medicinal chemistry and materials science, antibiotics, buffers, carbohydrates, enzymes, forensic tools, hematology and histology, nucleotides, proteins, peptides, amino acids and their derivatives.

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KEGG (tool)

RRID:SCR_012773

Integrated database resource consisting of 16 main databases, broadly categorized into systems information, genomic information, and chemical information. In particular, gene catalogs in completely sequenced genomes are linked to higher-level systemic functions of cell, organism, and ecosystem. Analysis tools are also available. KEGG may be used as reference knowledge base for biological interpretation of large-scale datasets generated by sequencing and other high-throughput experimental technologies.

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BD Biosciences (tool)

RRID:SCR_013311

An Antibody supplier

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Wako (tool)

RRID:SCR_013651

An Antibody supplier

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Skyline (tool)

RRID:SCR_014080

Software tool as Windows client application for targeted proteomics method creation and quantitative data analysis. Open source document editor for creating and analyzing targeted proteomics experiments. Used for large scale quantitative mass spectrometry studies in life sciences.

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C57BL/6J (tool)

RRID:IMSR_JAX:000664

Mus musculus with name C57BL/6J from IMSR.

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