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Proteasome inhibition and Tau proteolysis: an unexpected regulation
Author(s) -
Delobel P.,
Leroy O.,
Hamdane M.,
Sambo A.V.,
Delacourte A.,
Buée L.
Publication year - 2005
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2004.11.018
Subject(s) - proteasome , proteolysis , hyperphosphorylation , tau protein , microbiology and biotechnology , ubiquitin , tauopathy , neurodegeneration , chemistry , biology , alzheimer's disease , phosphorylation , biochemistry , neuroscience , disease , medicine , enzyme , gene
Increasing evidence suggests that an inhibition of the proteasome, as demonstrated in Parkinson's disease, might be involved in Alzheimer's disease. In this disease and other Tauopathies, Tau proteins are hyperphosphorylated and aggregated within degenerating neurons. In this state, Tau is also ubiquitinated, suggesting that the proteasome might be involved in Tau proteolysis. Thus, to investigate if proteasome inhibition leads to accumulation, hyperphosphorylation and aggregation of Tau, we used neuroblastoma cells overexpressing Tau proteins. Surprisingly, we showed that the inhibition of the proteasome led to a bidirectional degradation of Tau. Following this result, the cellular mechanisms that may degrade Tau were investigated.