Abstract
Neurosteroids are steroid hormones synthesised de novo in the brain and peripheral nervous tissues. In contrast to adrenal steroid hormones that act on intracellular nuclear receptors, neurosteroids directly modulate plasma membrane ion channels and regulate intracellular signalling. This review provides an overview of the work that led to the discovery of neurosteroids, our current understanding of their intracellular biosynthetic machinery, and their roles in regulating the development and function of nervous tissue. Neurosteroids mediate signalling in the brain via multiple mechanisms. Here, we describe in detail their effects on GABA (inhibitory) and NMDA (excitatory) receptors, two signalling pathways of opposing function. Furthermore, emerging evidence points to altered neurosteroid function and signalling in neurological disease. This review focuses on neurodegenerative diseases associated with altered neurosteroid metabolism, mainly Niemann-Pick type C, multiple sclerosis and Alzheimer disease. Finally, we summarise the use of natural and synthetic neurosteroids as current and emerging therapeutics alongside their potential use as disease biomarkers.
Highlights
that the brain is a site of de novo steroid biosynthesis
This means that the brain is a steroidogenic organ
these mostly act upon intracellular nuclear hormone receptors
Summary
From knowledge accrued over the past 30–40 years, that the brain is a site of de novo steroid biosynthesis [1,2]. Identification of neurons and glia of the CNS and PNS as sites of neurosteroid synthesis and function At the tissue level, various brain areas have been shown to express StAR, TSPO and the P450scc enzyme [52,53,54,55], which exert strong control over the production of pregnenolone. These enzymes form a complex to regulate the production of allopregnanolone, which is believed to be essential for the survival of Purkinje and granule neurons during cerebellar development [79,80] This observation of differential expression of neurosteroidogenic genes in different cells of the CNS may provide a mechanism for the generation and release of neurosteroids in order to mediate their extracellular signalling effects [81], which are discussed in more detail below. Any measurements may be clouded by the transfer of peripheral blood steroids into the brain [177], alongside the aforementioned potential for errors in measurement of some sulphated neurosteroids [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
