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Abstract

Tau is an axonal protein known to form abnormal aggregates and is the biomarker of Alzheimers disease. Metal-based therapeutics for inhibition of Tau aggregation is limited and rarely reported in the contemporary science. Here, the first example is reported of a rationally designed molecular cobalt(II)-complexes for effective inhibition of Tau and disaggregation of preformed Tau fibrils. The mechanistic studies revealed that the prevention of Tau aggregation by CBMCs is concentration-dependent and Tau seldom exhibits conformational changes. Interestingly, CBMCs play a dual role by causing disassembly of preformed aggregates as well as complete Tau inhibition. We believe that this unprecedented finding by the newly developed molecular complexes has a potential to lead to developing innovative metal-based therapeutics for Alzheimers disease.

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Kaleigh F. Roberts, Christopher R. Brue, Anna Preston+4 more·Journal of Inorganic Biochemistry·Oct 7, 2020· 12 citations