neuroesteroides

Neuroesteroides, commonly referred to as neurosteroids, are steroids synthesized in the brain and central nervous system. They can be produced de novo in neural tissue or derived from peripheral steroids that enter the CNS. Prominent examples include allopregnanolone (3α-hydroxy-5α-pregnan-3-one), pregnanolone, pregnenolone, and dehydroepiandrosterone (DHEA).

Biosynthesis starts from cholesterol. In mitochondria, cholesterol is converted to pregnenolone by P450scc (CYP11A1). Pregnenolone is a precursor to various neurosteroids through pathways involving 3β-HSD, 5α-reductase, and 3α-HSD. Allopregnanolone is produced from progesterone via 5α-reductase and 3α-HSD. DHEA and its downstream androgens can be formed via CYP17A1 enzymes. Brain cells express steroidogenic enzymes, enabling local synthesis independent of peripheral glands.

Most neuroesteroides act rapidly by modulating GABA_A receptors as positive allosteric modulators, enhancing inhibitory neurotransmission. Other targets include NMDA receptors, certain serotonin and sigma receptors, and membrane-associated signaling pathways. Unlike classical steroid hormones, many neuroesteroides exert non-genomic, fast effects and do not require nuclear receptor binding.

They influence neuronal excitability, synaptic plasticity, and neurogenesis, and play roles in stress response, mood regulation, learning, and memory. Altered neurosteroid levels have been linked to anxiety, depression, PTSD, epilepsy, and neurodegenerative diseases. Therapeutic applications include brexanolone, an allopregnanolone formulation approved for postpartum depression; ganaxolone for seizures; and other neurosteroid-based compounds in development.

Research areas include monitoring CNS levels, understanding regional synthesis, and developing targeted therapies with improved safety profiles.