01787nas a2200205   4500008004100000022001400041245008100055210006900136260000800205300001600213490000600229520106100235100002801296700002201324700003301346700003501379700002501414700003601439856010601475       2019                        eng d  a2470-134300aMolecular cobalt(II) complexes for tau polymerization in Alzheimer's disease0 aMolecular cobaltII complexes for tau polymerization in Alzheimer  cOCT  a16702-167140 v43 a<p>Tau is an axonal protein known to form abnormal aggregates and is the biomarker of Alzheimer's disease. Metal-based therapeutics for inhibition of Tau aggregation is limited and rarely reported in contemporary science. Here, we report the first example of rationally designed molecular cobalt(II)-complexes for effective inhibition of Tau and disaggregation of preformed Tau fibrils. The mechanistic studies reveal that prevention of Tau aggregation by cobalt-based metal complexes (CBMCs) is concentration-dependent and Tau seldom exhibits conformational changes. Interestingly, CBMCs play dual role in causing disassembly of preformed aggregates as well as inhibition of complete Tau aggregation. Furthermore, CBMCs were nontoxic and maintained the tubulin network intact. CBMCs also prevented okadaic acid-induced toxicity in SH-SY5Y cells thus, preventing hyperphosphorylation of Tau. We believe that this unprecedented finding by the newly developed molecular complexes has a potential toward metal-based therapeutics for Alzheimer's disease.</p>
1 aGorantla, Nalini, Vijay1 aLandge, Vinod, G.1 aNagaraju, Pramod, Gudigenaha1 aPriyadarshini, Poornima, C. G.1 aBalaraman, Ekambaram1 aChinnathambi, Subashchandrabose  uhttps://library.ncl.res.in/content/molecular-cobaltii-complexes-tau-polymerization-alzheimers-disease01853nas 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