%0 Journal Article %J Biochimica Et Biophysica Acta-General Subjects %D 2020 %T Melatonin interacts with repeat domain of Tau to mediate disaggregation of paired helical filaments %A Balmik, Abhishek Ankur %A Das, Rashmi %A Dangi, Abha %A Gorantla, Nalini Vijay %A Marelli, Udaya Kiran %A Chinnathambi, Subashchandrabose %K Alzheimer's disease %K Disaggregation %K melatonin %K Paired helical filaments %K tau protein %K Tauopathies %X

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 mu M 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.

%B Biochimica Et Biophysica Acta-General Subjects %V 1864 %P 129467 %8 MAR %G eng %9 Article %3

Foreign

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3.422

%R 10.1016/j.bbagen.2019.129467