Curcumin derivatives as metal-chelating agents: Implications for potential therapeutic agent for neurological disorders

The deposition of misfolded proteins, such as hyperphosphorylated tau, Amyloid  peptide, and more recently -synuclein, has been recognized as a feature of neurodegenerative diseases (NDD). Imbalances of metal ions concentration, especially copper and iron, may favor protein/peptide aggregation and subsequently trigger oxidative damage. Hence, metal chelators can play a key role in the exploration of neurological disorders pathogenesis and therapy. The “golden spice” Curcumin combines the interesting feature of strongly chelate metal ions through the keto-enolic moiety with several biological activities, among which antioxidant and anti-inflammatory. Trapping the metal ion by a sequestering agent like curcumin has at least three main goals: i) decrease in deposition and aggregation of misfolded proteins ii) reduce Fenton and Haber-Weiss reactions, iii) exploit intrinsic neuroprotection of ligand molecule. This chapter wants to be an up-to-date report and discussion on the most recent and promising studies on the role that curcumin-based chelators have in neuroprotection and in the development of therapeutic agents for neurological disorders.