Inflammation Induces TDP-43 Mislocalization and Aggregation.

Autor: Ana Sofia Correia, Priyanka Patel, Kallol Dutta, Jean-Pierre Julien
Jazyk: angličtina
Rok vydání: 2015
Předmět:
Zdroj: PLoS ONE, Vol 10, Iss 10, p e0140248 (2015)
Druh dokumentu: article
ISSN: 1932-6203
DOI: 10.1371/journal.pone.0140248
Popis: 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.
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