| http://purl.uniprot.org/citations/32393629 | http://www.w3.org/1999/02/22-rdf-syntax-ns#type | http://purl.uniprot.org/core/Journal_Citation |
| http://purl.uniprot.org/citations/32393629 | http://www.w3.org/2000/01/rdf-schema#comment | "Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are two related neurodegenerative diseases that present with similar TDP-43 pathology in patient tissue. TDP-43 is an RNA-binding protein which forms aggregates in neurons of ALS and FTD patients as well as in a subset of patients diagnosed with other neurodegenerative diseases. Despite our understanding that TDP-43 is essential for many aspects of RNA metabolism, it remains obscure how TDP-43 dysfunction contributes to neurodegeneration. Interestingly, altered neuronal dendritic morphology is a common theme among several neurological disorders and is thought to precede neurodegeneration. We previously found that both TDP-43 overexpression (OE) and knockdown (KD) result in reduced dendritic branching of cortical neurons. In this study, we used TRIBE (targets of RNA-binding proteins identified by editing) as an approach to identify signaling pathways that regulate dendritic branching downstream of TDP-43. We found that TDP-43 RNA targets are enriched for pathways that signal to the CREB transcription factor. We further found that TDP-43 dysfunction inhibits CREB activation and CREB transcriptional output, and restoring CREB signaling rescues defects in dendritic branching. Finally, we demonstrate, using RNA sequencing, that TDP-43 OE and KD cause similar changes in the abundance of specific messenger RNAs, consistent with their ability to produce similar morphological defects. Our data therefore provide a mechanism by which TDP-43 dysfunction interferes with dendritic branching, and may define pathways for therapeutic intervention in neurodegenerative diseases."xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://purl.org/dc/terms/identifier | "doi:10.1073/pnas.1917038117"xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://purl.uniprot.org/core/author | "Xu W."xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://purl.uniprot.org/core/author | "Rahman R."xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://purl.uniprot.org/core/author | "Rodal A.A."xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://purl.uniprot.org/core/author | "Rosbash M."xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://purl.uniprot.org/core/author | "Paradis S."xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://purl.uniprot.org/core/author | "Deshpande M."xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://purl.uniprot.org/core/author | "Herzog J.J."xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://purl.uniprot.org/core/author | "Suib H."xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://purl.uniprot.org/core/date | "2020"xsd:gYear |
| http://purl.uniprot.org/citations/32393629 | http://purl.uniprot.org/core/name | "Proc Natl Acad Sci U S A"xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://purl.uniprot.org/core/pages | "11760-11769"xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://purl.uniprot.org/core/title | "TDP-43 dysfunction restricts dendritic complexity by inhibiting CREB activation and altering gene expression."xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://purl.uniprot.org/core/volume | "117"xsd:string |
| http://purl.uniprot.org/citations/32393629 | http://www.w3.org/2004/02/skos/core#exactMatch | http://purl.uniprot.org/pubmed/32393629 |
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