Journal
NEUROBIOLOGY OF AGING
Volume 33, Issue 10, Pages 2291-2305Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.11.009
Keywords
Tau protein; Alzheimer's disease; Autophagy; Degradation
Categories
Funding
- EU/Memosad
- BMBF/KNDD
- Tau Consortium
- Hamburg LEXI Neurodapt
Ask authors/readers for more resources
Modulating the tau level may represent a therapeutic target for Alzheimer's disease (AD), as accumulating evidence shows that Abeta-induced neurodegeneration is mediated by tau. It is therefore important to understand the expression and degradation of tau in neurons. Recently we showed that overexpressed mutant tau and tau aggregates are degraded via the autophagic pathway in an N2a cell model. Here we investigated whether autophagy is involved in the degradation of endogenous tau in cultured primary neurons. We activated this pathway in primary neurons with trehalose, an enhancer of autophagy. This resulted in the reduction of endogenous tau protein. Tau phosphorylation at several sites elevated in AD pathology had little influence on its degradation by autophagy. Furthermore, by using a neuronal cell model of tauopathy, we showed that activation of autophagy suppresses tau aggregation and eliminates cytotoxicity. Notably, apart from activating autophagy, trehalose also inhibits tau aggregation directly. Thus, trehalose may be a good candidate for developing therapeutic strategies for AD and other tauopathies. (c) 2012 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available