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PLoS One. 2015 Oct 7;10(10):e0140248. doi: 10.1371/journal.pone.0140248. eCollection 2015.

Inflammation Induces TDP-43 Mislocalization and Aggregation.

Author information

1
Centre de Recherche du Centre Hospitalier Universitaire de Québec, 2705 Boulevard Laurier, Québec, QC, G1V 4G2, Canada.
2
Research Centre of Institut universitaire en santé mentale de Québec, Department of Psychiatry and Neuroscience, Laval University, Québec, QC, Canada.

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.

PMID:
26444430
PMCID:
PMC4596857
DOI:
10.1371/journal.pone.0140248
[Indexed for MEDLINE]
Free PMC Article

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