Brain-Delivery of Zinc-Ions as Potential Treatment for Neurological Diseases: Mini Review

Andreas      M. Grabrucker; Magali      Rowan; Craig      C. Garner

Abstract

Homeostasis of metal ions such as Zn2+ is essential for proper brain function. Moreover, the list of psychiatric and neurodegenerative disorders involving a dysregulation of brain Zn2+-levels is long and steadily growing, including Parkinsons and Alzheimers disease as well as schizophrenia, attention deficit and hyperactivity disorder, depression, amyotrophic lateral sclerosis, Downs syndrome, multiple sclerosis, Wilsons disease and Picks disease. Furthermore, alterations in Zn2+-levels are seen in transient forebrain ischemia, seizures, traumatic brain injury and alcoholism. Thus, the possibility of altering Zn2+-levels within the brain is emerging as a new target for the prevention and treatment of psychiatric and neurological diseases. Although the role of Zn2+ in the brain has been extensively studied over the past decades, methods for controlled regulation and manipulation of Zn2+ concentrations within the brain are still in their infancy. Since the use of dietary Zn2+ supplementation and restriction has major limitations, new methods and alternative approaches are currently under investigation, such as the use of intracranial infusion of Zn2+ chelators or nanoparticle technologies to elevate or decrease intracellular Zn2+ levels. Therefore, this review briefly summarizes the role of Zn2+ in psychiatric and neurodegenerative diseases and highlights key findings and impediments of brain Zn2+-level manipulation. Furthermore, some methods and compounds, such as metal ion chelation, redistribution and supplementation that are used to control brain Zn2+-levels in order to treat brain disorders are evaluated.

Keywords: Alzheimer, ’, s disease, ion chelators, nanoparticles, postsynaptic density, amyotrophic lateral sclerosis, zinc, nutrition, dietary zinc, epilepsy