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-disease