Inflammation Induces TDP-43 Mislocalization and Aggregation.

TitleInflammation Induces TDP-43 Mislocalization and Aggregation.
Publication TypeJournal Article
Year of Publication2015
AuteursCorreia, ASofia, Patel, P, Dutta, K, Julien, J-P
JournalPLoS One
Volume10
Issue10
Paginatione0140248
Date Published2015
ISSN1932-6203
KeywordsAnimals, Astrocytes, Cells, Cultured, DNA-Binding Proteins, Gene Expression Regulation, Humans, Inflammation, Lipopolysaccharides, Mice, Mice, Transgenic, Microglia, Point Mutation, Protein Aggregates, RNA, Messenger
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.

DOI10.1371/journal.pone.0140248
Alternate JournalPLoS ONE
PubMed ID26444430
PubMed Central IDPMC4596857
Grant List / / Canadian Institutes of Health Research / Canada