Chelation therapy for neurodegenerative diseases

Mounting evidence suggests a central role for transition biometals in the etiopathogenesis of neurodegenerative diseases (ND). Indeed, while studying the molecular basis for this heterogeneous group of diseases, it has become increasingly evident that biometals and nonphysiological Al are often involved in pathology onset and progression, either by affecting the conformation of specific proteins or by exacerbating local oxidative stress. The apparently critical role played by metal dishomeostasis in ND makes chelation therapy an attractive pharmacological option. However, classical metal chelation approaches, relying on potent metal ligands, turned out to be successful only in those rare cases where exceptional brain metal accumulation occurs due to specific defects in metal metabolism. In contrast, metal-targeted approaches using ligand of intermediate strength seem to be more appropriate in fighting the major ND, although their benefits are still questioned. We report here a survey of recent evidences supporting the use of a variety of metal ligands, and even functionalized nanoparticles, for the treatment of the most common ND. The beneficial neuropharmacological actions of metal-targeted agents most likely arise from local metal redistribution rather than from massive metal removal. The perspectives for the development of new effective agents against ND are critically discussed.