Using Small Molecules for Targeting Heavy Metals in Neurotoxicity and Neuroinflammation.

Abstract

Pharmaceutical drugs, natural toxins, industrial chemicals, and various environmental toxins negatively impact the nervous system. A significant cause of many neurodegenerative diseases is neurotoxicity. Although trace amounts of heavy metals are required for the proper functioning of several metabolic pathways, their dysregulation can cause many cellular and molecular alterations, which can enhance the risks associated with several neurodegenerative diseases. For example, high levels of heavy metals like manganese (Mn) affect the central nervous system with implications in both higher-order cognitive and motor functions. In addition, the buildup of amyloid aggregates and metal ions in the brain of patients with Alzheimer's disease is associated with disease pathogenesis. Small molecules capable of targeting neuroinflammation and neuroprotection pathways would be valuable to elucidate the pathological pathways associated with metal toxicity in neurogenerative disease. This chapter will summarize the necessary steps involved in (1) culturing of cell lines and maintenance of animal models, (2) design and preparation of samples of small molecules and treatment methodologies, (3) RNA and protein isolation and preparation of tissue and cell culture samples for quantitative studies, and (4) quantitative estimation of cellular products.