Molecules, Vol. 26, Pages 1175: Identification of Three Small Molecules That Can Selectively Influence Cellular Manganese Levels in a Mouse Striatal Cell Model

Molecules, Vol. 26, Pages 1175: Identification of Three Small Molecules That Can Selectively Influence Cellular Manganese Levels in a Mouse Striatal Cell Model Molecules doi: 10.3390/molecules26041175 Authors: Horning Tang Thomas Aschner Bowman Manganese (Mn) is a biologically essential metal, critical as a cofactor for numerous enzymes such a glutamine synthetase and kinases such as ataxia-telangiectasia mutated (ATM). Similar to other essential metals such as iron and zinc, proper levels of Mn need to be achieved while simultaneously being careful to avoid excess levels of Mn that can be neurotoxic. A lifetime of occupational exposure to Mn can often lead to a Parkinsonian condition, also known as “manganism”, characterized by impaired gait, muscle spasms, and tremors. Despite the importance of its regulation, the mechanisms underlying the transport and homeostasis of Mn are poorly understood. Rather than taking a protein or gene-targeted approach, our lab recently took a high-throughput-screening approach to identify 41 small molecules that could significantly increase or decrease intracellular Mn in a neuronal cell model. Here, we report characterization of these small molecules, which we refer to as the “Mn toolbox”. We adapted a Fura-2-based assay for measuring Mn concentration and for measuring relative concentrations of other divalent metals: nickel, copper, cobalt, and zinc. Of these 41 small molecules, we report here the identification o...
Source: Molecules - Category: Chemistry Authors: Tags: Article Source Type: research