Open Collections

Liu, Rui; Yang, Guang; Nonaka, Takashi; Arai, Tetsuaki; Jia, William; Cynader, Max S

BioMed Central

Background: TAR DNA-binding protein 43 (TDP-43) is a protein that is involved in the pathology of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Lobar Degeneration (FTLD). In patients with these neurodegenerative diseases, TDP-43 does not remain in its normal nuclear location, but instead forms insoluble aggregates in both the nucleus and cytoplasm of affected neurons. Results We used high density peptide array analysis to identify regions in TDP-43 that are bound by TDP-43 itself and designed candidate peptides that might be able to reduce TDP-43 aggregation. We found that two of the synthetic peptides identified with this approach could effectively inhibit the formation of TDP-43 protein aggregates in a concentration-dependent manner in HeLa cells in which a mutated human TDP-43 gene was overexpressed. However, despite reducing aggregation, these peptides did not reduce or prevent cell death. Similar results were observed in HeLa cells treated with arsenite. Again we found reduced aggregation, in this case of wild type TDP-43, but no difference in cell death. Conclusions Our results suggest that TDP-43 aggregation is associated with the cell death process rather than being a direct cause.

Article

eng

Vancouver : University of British Columbia Library

10.14288/1.0221294

Non UBC; Medicine, Faculty of

10.1186/2051-5960-1-49

Faculty

http://creativecommons.org/licenses/by/4.0/