Tau is the major neuronal protein involved in the stabilization of microtubule assembly. In Alzheimer's disease, Tau self-assembles to form intracellular protein aggregates which are toxic to cells. Various methods have been tried and tested to restrain the aggregation of Tau. Most of the agents tested for this purpose have limitations in their effectiveness and availability to neuronal cells. We have tested melatonin, a neurohormone secreted by pineal gland and a well-known anti-oxidant, for its ability to interact with the repeat domain of Tau using ITC and NMR. In aggregation inhibition and disaggregation studies of repeat Tau, melatonin was found to modulate the aggregation propensity of repeat Tau at a concentration of 5000 μM and was more effective in dissolving preformed aggregates rather than acting as an aggregation inhibitor. However, there were no major conformational changes in Tau in presence of melatonin as observed by CD spectroscopy. On the basis of our findings, we are proposing a mechanism by which melatonin can interact with the repeat domain of Tau and exhibit its disaggregation effect.

中文翻译：

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褪黑素与Tau的重复域相互作用，以介导成对的螺旋细丝的解聚。

Tau是参与微管装配稳定的主要神经元蛋白。在阿尔茨海默氏病中，Tau自组装形成对细胞有毒的细胞内蛋白质聚集体。已经尝试和测试了各种方法来抑制Tau的聚集。为此目的测试的大多数药剂在其有效性和对神经元细胞的可用性方面都有局限性。我们已经测试了褪黑激素（一种由松果体分泌的神经激素和一种著名的抗氧化剂），其利用ITC和NMR与Tau重复域相互作用的能力。在重复Tau的聚集抑制和解聚研究中，褪黑素被发现以5000μM的浓度调节重复Tau的聚集倾向，并且在溶解预先形成的聚集体方面比起聚集抑制剂更有效。然而，通过CD光谱法观察到，褪黑激素存在下Tau的构象没有重大变化。根据我们的发现，我们提出褪黑激素可以与Tau的重复域相互作用并发挥其分解作用的机制。