title: Inflammation Induces TDP-43 Mislocalization and Aggregation.
abstract: TAR DNA-binding protein 43 (TDP-43) is a major component in aggregates of ubiquitinated proteins in amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Here we report that lipopolysaccharide (LPS)-induced inflammation can promote TDP-43 mislocalization and aggregation. In culture, microglia and astrocytes exhibited TDP-43 mislocalization after exposure to LPS. Likewise, treatment of the motoneuron-like NSC-34 cells with TNF-alpha (TNF-α) increased the cytoplasmic levels of TDP-43. In addition, the chronic intraperitoneal injection of LPS at a dose of 1mg/kg in TDP-43(A315T) transgenic mice exacerbated the pathological TDP-43 accumulation in the cytoplasm of spinal motor neurons and it enhanced the levels of TDP-43 aggregation. These results suggest that inflammation may contribute to development or exacerbation of TDP-43 proteinopathies in neurodegenerative disorders.
authors.affiliation: Centre de Recherche du Centre Hospitalier Universitaire de Québec, 2705 Boulevard Laurier, Québec, QC, G1V 4G2, Canada.
authors.forename: Ana Sofia
authors.initials: AS
authors.lastname: Correia
authors.affiliation: Research Centre of Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Laval University, Québec, QC, Canada.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Patel
authors.affiliation: Research Centre of Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Laval University, Québec, QC, Canada.
authors.forename: Kallol
authors.initials: K
authors.lastname: Dutta
authors.affiliation: Research Centre of Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Laval University, Québec, QC, Canada.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Julien
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000235:genetics / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000276:immunology*; D008070:Lipopolysaccharides / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000276:immunology / Q000378:metabolism; D017354:Point Mutation; D066329:Protein Aggregates; D012333:RNA, Messenger / Q000235:genetics / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D008070:Lipopolysaccharides; D066329:Protein Aggregates; D012333:RNA, Messenger