About: Transcriptome–pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS

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About: Transcriptome–pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

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type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
title	Transcriptome–pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS
Creator	Madrigal, Assael Wang, Ruth Yeo, Gene Baughn, Michael Beate Winner, · Diaz-Garcia, Sandra Hutt, Kasey Kohl, Zacharias Krach, Florian Libby, Ryan Pirie, · Rabin, J Ranjan Batra, · Ravits, John Rodriguez, Maria Saberi, Shahram Stauffer, Jennifer Stuart, · Vu, Anthony Wheeler, Emily
source	PMC
abstract	Sporadic amyotrophic lateral sclerosis (sALS) is the most common form of ALS, however, the molecular mechanisms underlying cellular damage and motor neuron degeneration remain elusive. To identify molecular signatures of sALS we performed genome-wide expression profiling in laser capture microdissection-enriched surviving motor neurons (MNs) from lumbar spinal cords of sALS patients with rostral onset and caudal progression. After correcting for immunological background, we discover a highly specific gene expression signature for sALS that is associated with phosphorylated TDP-43 (pTDP-43) pathology. Transcriptome–pathology correlation identified casein kinase 1ε (CSNK1E) mRNA as tightly correlated to levels of pTDP-43 in sALS patients. Enhanced crosslinking and immunoprecipitation in human sALS patient- and healthy control-derived frontal cortex, revealed that TDP-43 binds directly to and regulates the expression of CSNK1E mRNA. Additionally, we were able to show that pTDP-43 itself binds RNA. CK1E, the protein product of CSNK1E, in turn interacts with TDP-43 and promotes cytoplasmic accumulation of pTDP-43 in human stem-cell-derived MNs. Pathological TDP-43 phosphorylation is therefore, reciprocally regulated by CK1E activity and TDP-43 RNA binding. Our framework of transcriptome–pathology correlations identifies candidate genes with relevance to novel mechanisms of neurodegeneration. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s00401-018-1870-7) contains supplementary material, which is available to authorized users.
has issue date	2018-06-07(xsd:dateTime)
bibo:doi	10.1007/s00401-018-1870-7
bibo:pmid	29881994
has license	no-cc
sha1sum (hex)	04b0af25530f43d89310833aec32dee6657f9b91
schema:url	https://doi.org/10.1007/s00401-018-1870-7
resource representing a document's title	Transcriptome–pathology correlation identifies interplay between TDP-43 and the expression of its kinase CK1E in sporadic ALS
has PubMed Central identifier	PMC6215775
has PubMed identifier	29881994
schema:publication	Acta Neuropathol
resource representing a document's body	covid:04b0af25530f43d89310833aec32dee6657f9b91#body_text
is schema:about of	named entity 'product' named entity 'background' named entity 'immunological' named entity 'CSNK1E' named entity 'TDP-43' named entity 'immunoprecipitation' named entity 'neuron' named entity 'expression' named entity 'lumbar' named entity 'amyotrophic lateral sclerosis' named entity 'regulates' named entity 'candidate' named entity 'promotes' named entity 'CK1E' named entity 'MNs' named entity 'performed' named entity 'CK1E' named entity 'activity' named entity 'binds' named entity 'interplay' named entity 'CSNK1E' named entity 'gene expression' named entity 'stem-cell' named entity 'correlation' named entity 'molecular mechanisms' named entity 'CSNK1E' named entity 'phosphorylated' named entity 'RNA' named entity 'ALS' named entity 'motor neurons' named entity 'sALS' named entity 'immunoprecipitation' named entity 'Sporadic amyotrophic lateral sclerosis' named entity 'pathology' named entity 'TDP-43' named entity 'kinase' named entity 'p62' named entity 'T-lymphocytes' named entity 'A303' named entity 'incubation' named entity 'cellular compartment' named entity 'RNA' named entity 'histologically' named entity 'postmortem' named entity 'mRNA' named entity 'striatum' named entity 'TDP-43' named entity 'gene expression' named entity 'CSNK1E' named entity 'formalin-fixed' named entity 'CSNK1E' named entity 'RNA' named entity 'antibody' named entity 'iPSC' named entity 'CSNK1E' named entity 'DMEM' named entity 'knock-down' named entity 'gene expression' named entity 'Addgene' named entity '5.11' named entity 'gene' named entity 'GraphPad Prism'

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