Proteasome inhibition and Tau proteolysis: an unexpected regulation.
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.
Delobel
P
P
INSERM U422, Institut de Médecine Prédictive et Recherche Thérapeutique, Place de Verdun, 59045, Lille, France. delobel@mrc-lmb.cam.ac.uk
Leroy
O
O
Hamdane
M
M
Sambo
A V
AV
Delacourte
A
A
Buée
L
L
D000544:Alzheimer Disease / Q000378:metabolism*; D045163:Antibodies, Phospho-Specific / Q000276:immunology; D020169:Caspases / Q000032:analysis / Q000378:metabolism; D002457:Cell Extracts / Q000737:chemistry; D045744:Cell Line, Tumor; D006801:Humans; D007976:Leupeptins / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D010766:Phosphorylation; D011065:Poly(ADP-ribose) Polymerases / Q000032:analysis / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000032:analysis / Q000502:physiology*; D061988:Proteasome Inhibitors; D016875:tau Proteins / Q000032:analysis / Q000378:metabolism*
D045163:Antibodies, Phospho-Specific; D002457:Cell Extracts; D007976:Leupeptins; D061988:Proteasome Inhibitors; D016875:tau Proteins; D011065:Poly(ADP-ribose) Polymerases; D020169:Caspases; D046988:Proteasome Endopeptidase Complex; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde