Neurosteroidogenesis Today: Novel Targets for Neuroactive Steroid Synthesis and Action and Their Relevance for Translational Research

The 2016 document reviews the significance of neuroactive steroids, which are synthesized in the brain and can influence neuronal excitability and gene expression, and their therapeutic potential for neuropsychiatric and neurodegenerative diseases. It notes that neurosteroidogenesis is dysregulated in various disorders, including depression, PTSD, schizophrenia, bipolar disorder, and alcoholism, as well as in patients with male pattern hair loss treated with finasteride. The review suggests that modulating neurosteroidogenesis could be a more effective treatment than direct administration of neuroactive steroids due to challenges like low bioavailability and potential side effects. It highlights the translocator protein (TSPO) and the pregnane xenobiotic receptor (PXR) as novel targets for promoting neurosteroidogenesis, which could lead to new therapies for Alzheimer's disease and other conditions. The document also includes a study on transgenic mice that showed changes in behavior and steroid concentrations after progesterone administration, suggesting the importance of neuroactive steroid homeostasis for brain health. Additionally, it discusses the role of neuroactive steroids in alcohol-related behaviors in rats and mice, and the potential for targeting neurosteroidogenesis as a therapeutic approach for alcoholism.