Neurosteroids in Neurological and Psychiatric Disorders: Therapeutic Implications

CNS Neurol Disord Drug Targets. 2026 Mar 12. doi: 10.2174/0118715273411580251203115939. Online ahead of print.

ABSTRACT

Neurosteroids play a significant role in brain functions with substantial implications for mood regulation, seizure susceptibility, stress response, and potential therapeutic applications. However, dysregulation of steroidogenesis and its signalling is associated with various neurological and psychiatric disorders, such as major depressive disorder, schizophrenia, tourette syndrome and post-traumatic stress disorder, with altered levels of neuroactive steroids contributing to these conditions. Neurosteroids can counteract the effects of stress by enhancing GABAergic inhibition, thereby helping to maintain emotional homeostasis. Furthermore, neuroinflammatory processes linked to neurodegenerative diseases, including Alzheimer’s and Parkinson’s, can disrupt neurosteroid synthesis. The potential for therapeutic modulation of neurosteroid biosynthesis via ligands targeting steroidogenic pathways offers an exciting avenue for treatment. Despite the promise of neuroactive steroids, their rapid metabolism and low oral bioavailability pose significant challenges. Consequently, extensive research is now focused on developing synthetic analogues and modulators that can modulate neuroactive steroid synthesis and metabolism. This review is based on an understanding of neuroactive steroids and their role in neurological disorders.

PMID:41833033 | DOI:10.2174/0118715273411580251203115939