Fig.1.

Intermediate and final limonoids decrease aggregation of tau. A,B) The final limonoids were isolated from neem kernel of Azadirachta indica and the structure of nimbin and salannin. C) The full-length tau (hTau40 wt) is composed of 441 amino acids and has two inserts towards the N-terminal. The number of inserts vary from 0 to 2 based on the isoforms. This is followed by a proline rich region which is known to involve in interaction with various proteins such as microtubule, kinases, etc. The four repeats towards the C-terminal are also known as microtubule-binding domain, named on the basis of its function. Tau undergoes alternative splicing and results in six isoforms which have either three or four repeats. The expression of these isoforms is developmentally regulated and is altered during AD pathology. D, E) The inhibition of full-length tau aggregation by nimbin and salannin was probed by ThS fluorescence and plotted in terms of percentage inhibition at 120 h. F) The aggregation inhibition in terms of percentage was plotted. It indicated that nimbin and salannin showed similar effects in inhibiting tau aggregation. G) In in vitro condition heparin induces tau aggregation into thick and extended fibril like structure. H, I) The presence of nimbin and salannin prevents extensive aggregation of tau and instead leads to the formation of thin, short, and fragile aggregates. The significance was calculated using SigmaPlot 10.0 and ***, ** and * indicates p value <0.001, <0.01 and <0.05 respectively. ns is not significant where p≥0.05.