title: Calcium-engaged Mechanisms of Nongenomic Action of Neurosteroids.
abstract: BACKGROUND
  Neurosteroids form the unique group because of their dual mechanism of action. Classically, they bind to specific intracellular and/or nuclear receptors, and next modify genes transcription. Another mode of action is linked with the rapid effects induced at the plasma membrane level within seconds or milliseconds. The key molecules in neurotransmission are calcium ions, thereby we focus on the recent advances in understanding of complex signaling crosstalk between action of neurosteroids and calcium-engaged events.
  
  
  METHODS
  Short-time effects of neurosteroids action have been reviewed for GABAA receptor complex, glycine receptor, NMDA receptor, AMPA receptor, G protein-coupled receptors and sigma-1 receptor, as well as for several membrane ion channels and plasma membrane enzymes, based on available published research.
  
  
  RESULTS
  The physiological relevance of neurosteroids results from the fact that they can be synthesized and accumulated in the central nervous system, independently from peripheral sources. Fast action of neurosteroids is a prerequisite for genomic effects and these early events can significantly modify intracellular downstream signaling pathways. Since they may exert either positive or negative effects on calcium homeostasis, their role in monitoring of spatio-temporal Ca2+ dynamics, and subsequently, Ca2+-dependent physiological processes or initiation of pathological events, is evident.
  
  
  CONCLUSIONS
  Neurosteroids and calcium appear to be the integrated elements of signaling systems in neuronal cells under physiological and pathological conditions. A better understanding of cellular and molecular mechanisms of nongenomic, calcium-engaged neurosteroids action could open new ways for therapeutic interventions aimed to restore neuronal function in many neurological and psychiatric diseases.
authors.affiliation: Department of Molecular Neurochemistry, Faculty of Health Sciences, Medical University of Lodz, Poland.
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Rebas
authors.affiliation: Department of Molecular Neurochemistry, Faculty of Health Sciences, Medical University of Lodz, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Radzik
authors.affiliation: Department of Molecular Neurochemistry, Faculty of Health Sciences, Medical University of Lodz, Poland.|Boston Children's Hospital and Harvard Medical School, Boston, USA.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Boczek
authors.affiliation: Department of Molecular Neurochemistry, Faculty of Health Sciences, Medical University of Lodz, Poland.
authors.forename: Ludmila
authors.initials: L
authors.lastname: Zylinska
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism*; D006801:Humans; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects*
chemical_list: D018377:Neurotransmitter Agents; D011956:Receptors, Cell Surface; D002118:Calcium
keywords: Calcium; central nervous system; neuropathology.; neuroprotection; neurosteroids; nongenomic action