S. Feuillette and O. Blard contributed equally to this work.
Tau is not normally degraded by the proteasome
Version of Record online: 28 MAR 2005
Copyright © 2005 Wiley-Liss, Inc.
Journal of Neuroscience Research
Volume 80, Issue 3, pages 400–405, 1 May 2005
How to Cite
Feuillette, S., Blard, O., Lecourtois, M., Frébourg, T., Campion, D. and Dumanchin, C. (2005), Tau is not normally degraded by the proteasome. J. Neurosci. Res., 80: 400–405. doi: 10.1002/jnr.20414
- Issue online: 31 MAR 2005
- Version of Record online: 28 MAR 2005
- Manuscript Accepted: 30 NOV 2004
- Manuscript Revised: 29 NOV 2004
- Manuscript Received: 26 JUL 2004
- Aventis Pharma
- France Alzheimer Finistère
- Conseil Régional de Haute-Normandie
- Alzheimer's disease;
Tau-positive inclusions in neurons are consistent neuropathologic features of the most common causes of dementias such Alzheimer's disease and frontotemporal dementia. Ubiquitinated tau-positive inclusions have been reported in brains of Alzheimer's disease patients, but involvement of the ubiquitin-dependent proteasomal system in tau degradation remains controversial. Before considering the tau degradation in pathologic conditions, it is important to determine whether or not endogenous tau is normally degraded by the proteasome pathway. We therefore investigated this question using two complementary approaches in vitro and in vivo. Firstly, SH-SY5Y human neuroblastoma cells were treated with different proteasome inhibitors, MG132, lactacystin, and epoxomicin. Under these conditions, neither total nor phosphorylated endogenous tau protein levels were increased. Instead, an unexpected decrease of tau protein was observed. Secondly, we took advantage of a temperature-sensitive mutant allele of the 20S proteasome in Drosophila. Genetic inactivation of the proteasome also resulted in a decrease of tau levels in Drosophila. These results obtained in vitro and in vivo demonstrate that endogenous tau is not normally degraded by the proteasome. © 2005 Wiley-Liss, Inc.