Effects of neurosteroids on neuronal survival: Molecular basis and clinical perspectives

Abstract

Neurosteroids have long been known to act as important modulators of central nervous system functions. The concept of their mechanism of action, however, have essentially undergone an evolution. Previously, these compounds were postulated to regulate neuronal function mainly via allosteric regulation of some membrane-bound receptors, such as GABAA and NMDA receptors, in a non-genomic way. Recent studies have provided evidence for intracellular targets for neurosteroids, e.g., transcription factors (NFκ-B, progesterone receptors), protein kinases (phosphatidylinositol 3-kinase, protein kinase C), or microtubule-associated proteins, i.e. factors essential in regulation of neuronal survival and apoptosis. This paper reviews in vitro and in vivo data on neurosteroid involvement in the regulation of neurodegenerative processes with emphasis on new intracellular and genomic mechanisms of their action. Potential utility of neurosteroids in the treatment of some neurodegenerative disorders has been also discussed.