Partial loss of TDP-43 function causes phenotypes of amyotrophic lateral sclerosis
Abstract
Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease that causes paralysis and death. TDP-43 is a protein that regulates gene expression. TDP-43 aggregation and depletion from cell nucleus are found in ALS. Therefore, TDP-43 may cause neurodegeneration by generating toxicity from its aggregation or by a loss of its function. Our experiments test the consequence of a partial loss of TDP-43 function in mice. The results demonstrate that a partial loss of TDP-43 function is sufficient to cause neurodegeneration and ALS symptoms. In addition, we have found evidence for TDP-43 dysfunction in human ALS. Therefore, we propose that TDP-43 dysfunction causes neurodegeneration in the human disease, and future therapy should aim to restore the normal function of TDP-43.
- Publication:
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Proceedings of the National Academy of Science
- Pub Date:
- March 2014
- DOI:
- 10.1073/pnas.1322641111
- Bibcode:
- 2014PNAS..111E1121Y