Neurosteroids are a group of steroid hormones synthesized by the brain in the presence of steroidogenic enzymes. Specific neurosteroids modulate function of several receptors, and also regulate growth of neurons, myelinization and synaptogenesis in the central nervous system. Some neurosteroids have been shown to display neuroprotective properties, which may have important implications for their potential use in the treatment of various neuropathologies such as: age-dependent dementia, stroke, epilepsy, spinal cord injury, Alzheimer's disease (AD), Parkinson's disease (PD) and Niemann-Pick type C disease (NP-C). This paper focuses on neuroprotection afforded by neurosteroids.
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Nat Struct Mol Biol
January 2025
Department of Biochemistry, Duke University School of Medicine, Durham, NC, USA.
Transient receptor potential channel subfamily M member 3 (TRPM3) is a Ca-permeable cation channel activated by the neurosteroid pregnenolone sulfate (PregS) or heat, serving as a nociceptor in the peripheral sensory system. Recent discoveries of autosomal dominant neurodevelopmental disorders caused by gain-of-function mutations in TRPM3 highlight its role in the central nervous system. Notably, the TRPM3 inhibitor primidone, an anticonvulsant, has proven effective in treating patients with TRPM3-linked neurological disorders and in mouse models of thermal nociception.
View Article and Find Full Text PDFBiochim Biophys Acta Mol Basis Dis
January 2025
Department of Internal Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Neurology, Departments of School of Medicine, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Public Health Department of Graduate School of Biomedical Sciences, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Speech, Language and Hearing Sciences, School Health Professions, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA; Department of Pharmacology and Neuroscience, Texas Tech University Health Sciences Center, Lubbock, TX 79430, USA.
Alzheimer's disease (AD)-related dementia preferentially impacts two-thirds of women and one-third of men. The steroidogenic acute regulatory (StAR) protein mediates the biosynthesis of neurosteroids that sustain diverse neuronal activities. Aging, involving neurosteroidal imbalance, is the predominant risk factor for AD causing dementia.
View Article and Find Full Text PDFQ Rev Biophys
January 2025
Faculty of Medicine, Department of Biophysics and Neuroscience, Wroclaw Medical University, Wrocław, Poland.
The GABA type A receptor (GABAR) belongs to the family of pentameric ligand-gated ion channels and plays a key role in inhibition in adult mammalian brains. Dysfunction of this macromolecule may lead to epilepsy, anxiety disorders, autism, depression, and schizophrenia. GABAR is also a target for multiple physiologically and clinically relevant modulators, such as benzodiazepines (BDZs), general anesthetics, and neurosteroids.
View Article and Find Full Text PDFKorean J Physiol Pharmacol
January 2025
Department of Pharmacology, Catholic Kwandong University College of Medicine, Gangneung 25601, Korea.
Neurosteroids play an important role as endogenous neuromodulators that are locally produced in the central nervous system and rapidly change the excitability of neurons and the activation of microglial cells and astrocytes. Here we review the mechanisms of synthesis, metabolism, and actions of neurosteroids in the central nervous system. Neurosteroids are able to play a variety of roles in the central nervous system under physiological conditions by binding to membrane ion channels and receptors such as gamma-aminobutyric acid type A receptors, Nmethyl- D-aspartate receptors, L- and T-type calcium channels, and sigma-1 receptors.
View Article and Find Full Text PDFJ Dev Orig Health Dis
January 2025
School of Biomedical Sciences and Pharmacy, University of Newcastle, Newcastle, Australia.
Preterm birth exposes the neonate to hypoxic-ischaemic and excitotoxic insults that impair neurodevelopment and are magnified by the premature loss of placentally supplied, inhibitory neurosteroids. The cerebellum is a neuronally dense brain region, which undergoes critical periods of development during late gestation, when preterm births frequently occur. We propose that neurosteroid replacement therapy using tiagabine and zuranolone will protect the cerebellum against preterm-associated insults.
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