The main neurodegenerative diseases, such as Alzheimer′s, Parkinson′s, Huntington′s, amyotrophic lateral sclerosis (ALS) and Prion diseases, present certain similarities, as in the aggregation of disease-specific proteins in the central nervous system (CNS). All these proteins have been shown to interact with metal ions with redox activity. Biometals like copper, iron, manganese, and zinc are crucial for many physiological functions, especially in the CNS. However, at the cerebral level, shifts in the amounts of these metals can lead to the excessive production of reactive oxygen species (ROS), like H2O2 and hydroxyl radicals, and of reactive nitrogen species (RNS), like NO. These free radicals are toxic and, if not removed or neutralized, they react with lipids, proteins, and nucleic acids, damaging several cellular functions, contributing to the intensification of oxidative stress. Toxic metals like aluminum and lead are mainly absorbed and captured by the brain. Unlike biometals, the organism cannot provide homeostatic regulation of toxic metals. These metals exert their toxic effects by competing with essential metals for an active enzyme or a membrane protein sites and by intense reacting with biologically active groups. This Special Issue will focus on metal toxicity and nervous system disorders, the main related pathogenic mechanisms, and possible therapeutic strategies.
Prof. Dr. Fernanda Leal
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