Molecular Cobalt(II) Complexes for Tau Polymerization in Alzheimer’s Disease.

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.