Physiological Metals Can Induce Conformational Changes in Transthyretin Structure: Neuroprotection or Misfolding Induction?

Transthyretin (TTR) is a plasma homotetrameric protein that transports thyroxine and retinol. TTR itself, under pathological conditions, dissociates into partially unfolded monomers aggregate form fibrils. Metal ions such as Zn2+, Cu2+, Fe2+, Mn2+ Ca2+ play controversial role in the amyloidogenic pathway. also present cerebrospinal fluid (CSF), where it behaves one of major A?-binding-proteins. The interaction between A? stronger presence high concentrations Cu2+. Crystals TTR, soaked solutions physiological metals Cu2+ but not Mn2+, Fe3+, Al3+, Ni2+, revealed an unusual conformational change. Here, we investigate effects have on order to understand if can induce specific active conformation guides its A?-scavenging role. capability certain accelerate process discussed.