02228nas a2200217   4500008004100000022001400041245006100055210006100116260000800177300001400185490000700199520152900206653003201735653002901767653002001796653001801816653001601834100003401850700003601884856009001920       2022                        eng d  a0739-110200aRole of cysteines in accelerating Tau filament formation0 aRole of cysteines in accelerating Tau filament formation  cJUN  a4366-43750 v403 a<p>
	Alzheimer's disease is majorly associated with intracellular accumulation of Tau into paired helical filaments and tangles. The self-aggregated dimeric and oligomeric species of Tau formed are more toxic to neuronal cells and acts as seeds for filament formation. The two cysteine residues and the two hexapeptide regions of full-length Tau play a key role in initialization and filament formation during Tau aggregation. The role of cysteine residues in Tau aggregation has been studied by in-vitro aggregation assay that was measured by Thioflavin S fluorescence to observe the kinetics of aggregation. In this study, we have performed in-vitro aggregation assay with recombinant full-length Tau and the cysteine mutants to understand the mechanism of cysteine independent Tau aggregation. Here, we report that cysteine mutant full-length Tau can aggregate to form filaments under in-vitro conditions. To visualize the polymorphisms of Tau and cysteine mutants under different aggregation conditions anionic cofactor, heparin was employed. Wild-type Tau showed rapid aggregation to form oligomers and filaments. On the other hand, the cysteine mutant delayed the initial Tau aggregation. This indicates the importance of cysteine residues in accelerating initial Tau nucleation for its aggregation. The filament morphology of wild-type and cysteine mutant Tau has been characterized using transmission electron microscopy and high-resolution transmission electron microscopy. Communicated by Ramaswamy H. Sarma</p>
10aHeparin-induced aggregation10aPaired helical filaments10aTau Aggregation10aTau Oligomers10atau protein1 aChidambaram, Hariharakrishnan1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/role-cysteines-accelerating-tau-filament-formation