@article {46945,
	title = {Melatonin interacts with repeat domain of Tau to mediate disaggregation of paired helical filaments},
	journal = {Biochimica Et Biophysica Acta-General Subjects},
	volume = {1864},
	year = {2020},
	month = {MAR},
	pages = {129467},
	type = {Article},
	abstract = {<p>Tau is the major neuronal protein involved in the stabilization of microtubule assembly. In Alzheimer{\textquoteright}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.</p>
},
	keywords = {Alzheimer{\textquoteright}s disease, Disaggregation, melatonin, Paired helical filaments, tau protein, Tauopathies},
	issn = {0304-4165},
	doi = {10.1016/j.bbagen.2019.129467},
	author = {Balmik, Abhishek Ankur and Das, Rashmi and Dangi, Abha and Gorantla, Nalini Vijay and Marelli, Udaya Kiran and Chinnathambi, Subashchandrabose}
}
@article {49200,
	title = {Macrocyclic peptides derived from AcPHF6*and AcPHF6 to selectively modulate the Tau aggregation},
	journal = {Bioorganic Chemistry},
	volume = {151},
	year = {2024},
	month = {OCT},
	pages = {107625},
	type = {Article},
	abstract = {<p>
	Ten macrocyclic peptides, each comprising 14 amino acids, were designed and synthesized based on the Tau aggregation model hexapeptides AcPHF6* and AcPHF6. The design took into account the aggregation tendencies of each residue in AcPHF6* and AcPHF6, their aggregation models, while employing peptide-based structural design principles including N-methylation to promote turns and to block hydrogen bond propagation and elongation of the aggregation chain. NMR analysis supported that all these peptides adopted an antiparallel beta-sheet conformation. Self-aggregation studies characterized the aggregation properties of these peptides, identifying two peptides with the highest (P3) and lowest (P8) aggregation tendencies. In cross-aggregation studies with the parent peptides AcPHF6* and AcPHF6, P3 and P8 were found to promote and reduce aggregation, respectively. Furthermore, P3 and P8 demonstrated an enhancement and diminution effect on the aggregation of K18wt, indicating their capacity to modulate aggregation even at the macromolecular level. Thus, the two simple peptides, P3 and P8 selectively exhibit pro- or anti-aggregation effects on PHF peptides and Tau. This study, has thus developed structurally well-defined non-complex peptides, derived from AcPHF6* and AcPHF6, to modulate Tau aggregation as desired, offering applications in Tau model studies and the development of Tau aggregation inhibitors or promoters.</p>
},
	keywords = {Cyclic peptides, Peptide -based drug design (PBDD), Peptide conformation, PHF peptides, Tau Aggregation},
	issn = {0045-2068},
	doi = {10.1016/j.bioorg.2024.107625},
	author = {Dangi, Abha and Qureshi, Tazeen and Chinnathambi, Subashchandrabose and Marelli, Udaya Kiran}
}
