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Acta Neuropathologica Communications

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Open Access 01-12-2013 | Research

Reducing TDP-43 aggregation does not prevent its cytotoxicity

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

Published in: Acta Neuropathologica Communications | Issue 1/2013

Abstract

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.

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Title: Reducing TDP-43 aggregation does not prevent its cytotoxicity
Authors: Rui Liu
Guang Yang
Takashi Nonaka
Tetsuaki Arai
William Jia
Max S Cynader
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Acta Neuropathologica Communications / Issue 1/2013
Electronic ISSN: 2051-5960
DOI: https://doi.org/10.1186/2051-5960-1-49

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Springer Medicine

Reducing TDP-43 aggregation does not prevent its cytotoxicity

Abstract

Background

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusions

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