02051nas a2200229   4500008004100000022001400041245009500055210006900150260000900219300001200228490000800240520126000248653002401508653002401532653002001556653001901576653001701595100002101612700002501633700003601658856012701694       2020                        eng d  a0141-813000aCobalt-based metal complexes prevent repeat tau aggregation and nontoxic to neuronal cells0 aCobaltbased metal complexes prevent repeat tau aggregation and n  cJUN   a171-1790 v1523 a<p>Alzheimer's disease (AD) is a fatal neurodegenerative disorder with an alarming increase in the death rate every year. AD is characterised by an aberrant accumulation of proteins in the form of aggregates. The axonal microtubule-associated protein Tau and arnyloid-beta undergo structural transition to beta-sheet rich structure and form aggregates in neuronal soma as well as in the extracellular region. The loss of Tau from microtubules leads to the disintegration of axon and causing neuronal degeneration. This led to the development of effective drugs against AD, to prevent Tau aggregation. Here, we synthesized and screen metal-based complexes to prevent Tau protein aggregation. ThS fluorescence and TEM suggested the role of synthetic cobalt complexes in inhibiting Tau aggregation. CD spectroscopy showed that these complexes prevented conformational changes in Tau to beta-sheet. CBMCs were not toxic at lower concentrations and formed non-toxic Tau species. L1 and L2 prevented membrane leakage: whereas, higher concentrations of L3 caused membrane leakage as observed by LDH release assay. The overall results indicate the synthetic cobalt complexes to be a promising molecule against AD. (C) 2020 Elsevier B.V. All rights reserved.</p>
10aAlzheimer's disease10aCobalt-based metals10aTau Aggregation10aTau inhibition10aTau toxicity1 aGorantla, Nalini1 aBalaraman, Ekambaram1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/cobalt-based-metal-complexes-prevent-repeat-tau-aggregation-and-nontoxic-neuronal-cells01853nas a2200217   4500008004100000022001400041245006600055210006400121260000900185300001600194490000600210520113100216100002101347700002101368700002201389700002501411700003501436700002701471700003601498856010101534       2021                        eng d  a2470-134300aAmyloid-beta-derived peptidomimetics inhibits tau aggregation0 aAmyloidbetaderived peptidomimetics inhibits tau aggregation  cMAY   a11131-111380 v63 a<p>The aggregation of tau protein is one of the hallmarks for Alzheimer's disease, resulting in neurodegeneration. The peptidomimetics strategy to prevent tau aggregation is more specific over other small molecules. In the present study, we analyzed the effect of amyloid-beta-derived peptidomimetics for inhibiting heparin-induced tau aggregation in vitro. These peptides and their derivatives were known to prevent aggregation of amyloid-beta. KLVFF is a hydrophobic sequence of the pentapeptide that prevented tau aggregation as observed by thioflavin S fluorescence, transmission electron microscopy, and circular dichroism spectroscopy. P4 and P5 also prevented assembly of tau into aggregates and formed short fibrils. The beta-sheet breaker LPFFD was however ineffective in preventing tau aggregation. The peptides further demonstrated reversal of tau-induced cytotoxicity in a dose-dependent manner. Our results suggested that these peptides can also be used to inhibit tau aggregation and also, toxicity induced by tau could be considered as potential molecules that have an effect on tau as well as amyloid-beta.</p>1 aGorantla, Nalini1 aSunny, Lisni, P.1 aRajasekhar, Kolla1 aNagaraju, Pramod, G.1 aPriyadarshini, Poornima, C. G.1 aGovindaraju, Thimmaiah1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/amyloid-beta-derived-peptidomimetics-inhibits-tau-aggregation