Selenium and selenoproteins in neuroprotection and neuronal cell death

Abstract

Significant progress has taken place in the field of selenium neurobiology since the discovery of selenocy steine as the 21st genetically coded amino acid. Twenty-five selenoproteins playing important roles in various processes of redox signalling have been identified in the human genome to date, which is why these proteins are also called selenoenzymes. The function of all selenoproteins is dictated by the trace element selenium. Its depletion is therefore detrimental to selenoprotein activity, leading to increased oxidative stress and adversely affecting neuronal cell survival. Oxidative stress constitutes one of the underlying pathological processes in acute neurodegenerative diseases such as stroke and epilepsy, as well as in chronic processes such as Parkinson's and Alzheimer's diseases. Selenium, as well as many selenoproteins like glutathione peroxidases (GPx), thioredoxin reductases and selenoprotein M are involved in antioxidant defence and the maintenance of intracellular redox balance. Research in molecular biology and gene targeting in mice has led to the discovery of the essential role of selenoproteins in neuronal cell functioning. The available data on selenium and selenoproteins with regard to neuronal cell death are summarized and potential therapeutic targets in neuroprotective approaches in conditions of human disease discussed.