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Biosynthesis and signalling functions of central and peripheral nervous system neurosteroids in health and disease

Lloyd-Evans, Emyr and Waller-Evans, Helen 2020. Biosynthesis and signalling functions of central and peripheral nervous system neurosteroids in health and disease. Essays in Biochemistry 64 (3) , pp. 591-606. 10.1042/EBC20200043

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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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Biosciences
Publisher: Portland Press
ISSN: 0071-1365
Date of First Compliant Deposit: 1 September 2020
Date of Acceptance: 14 July 2020
Last Modified: 04 Nov 2020 14:26
URI: http://orca.cf.ac.uk/id/eprint/134588

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