Degradation of TDP-43 and its pathogenic form by autophagy and the ubiquitin-proteasome system - PubMed (original) (raw)
. 2010 Jan 18;469(1):112-6.
doi: 10.1016/j.neulet.2009.11.055. Epub 2009 Nov 26.
Affiliations
- PMID: 19944744
- DOI: 10.1016/j.neulet.2009.11.055
Degradation of TDP-43 and its pathogenic form by autophagy and the ubiquitin-proteasome system
Xiaoju Wang et al. Neurosci Lett. 2010.
Abstract
TAR DNA-binding protein-43 (TDP-43) is a nuclear protein functioning in the regulation of transcription and mRNA splicing. TDP-43 is accumulated in ubiquitinated inclusions in frontotemporal lobar degeneration with ubiquitin-positive inclusions (FTLD-U) and amyotrophic lateral sclerosis (ALS) diseased brains. However, the pathways involved in the clearance of TDP-43 and its pathogenic form (TDP-25), a truncated form of TDP-43, are still not elucidated. In this study, we demonstrated that the protein levels of TDP-43 and TDP-25 were increased in cells treated with a proteasome inhibitor, MG132, or an autophagy inhibitor, 3-MA, whereas, they were decreased in cells treated with an enhancer of autophagy, trehalose. Furthermore, more protein level changes of TDP-25 than TDP-43 were observed in cells treated with above inhibitors or enhancer. Thus, our data suggest that TDP-43 and TDP-25 are degraded by both proteasome and autophagy with TDP-25 being more regulated.
(c) 2009 Elsevier Ireland Ltd. All rights reserved.
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