Delobel P, Leroy O, Hamdane M, Sambo A V, Delacourte A, Buée L
INSERM U422, Institut de Médecine Prédictive et Recherche Thérapeutique, Place de Verdun, 59045, Lille, France.
FEBS Lett. 2005 Jan 3;579(1):1-5. doi: 10.1016/j.febslet.2004.11.018.
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.
越来越多的证据表明，如在帕金森病中所证实的那样，蛋白酶体的抑制可能与阿尔茨海默病有关。在这种疾病及其他 Tau 蛋白病中，Tau 蛋白在退化的神经元内发生过度磷酸化并聚集。在这种状态下，Tau 蛋白也会被泛素化，这表明蛋白酶体可能参与 Tau 蛋白的水解。因此，为了研究蛋白酶体抑制是否会导致 Tau 蛋白的积累、过度磷酸化和聚集，我们使用了过表达 Tau 蛋白的神经母细胞瘤细胞。令人惊讶的是，我们发现蛋白酶体的抑制导致了 Tau 蛋白的双向降解。基于这一结果，我们对可能降解 Tau 蛋白的细胞机制进行了研究。
