Inflammation Induces TDP-43 Mislocalization and Aggregation |
| |
Authors: | Ana Sofia Correia Priyanka Patel Kallol Dutta Jean-Pierre Julien |
| |
Affiliation: | 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, ; Department of Pathology, Anatomy & Cell Biology, Thomas Jefferson University, UNITED STATES, |
| |
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-43A315T 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. |
| |
Keywords: | |
|
|