Send to

Choose Destination
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

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


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.

[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Public Library of Science Icon for PubMed Central
Loading ...
Support Center