Levels and actions of neuroactive steroids in the nervous system under physiological and pathological conditions: Sex-specific features

• Neuroactive steroids are involved in the physiological regulation of brain function.
• Neuroactive steroids participate in the control of mood, behavior and cognition.
• Neuroactive steroids exert neuroprotective actions.
• The levels of neuroactive steroids are different in males and females.
• CNS and PNS pathology regulates neuroactive steroids in a sex-dependent manner.

Neuroactive steroids regulate the physiology of the central and peripheral nervous system, exert neuroprotective actions and represent interesting tools for therapeutic strategies against neurodegenerative and psychiatric disorders. Sex differences in their levels are detected not only under physiological conditions but are also modified in a sex-dependent way in different pathological alterations such as Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, traumatic brain injury, spinal cord injury, stroke, diabetic encephalopathy, psychiatric disorders and peripheral neuropathy. Interestingly, many of these disorders show sex differences in their incidence, symptomatology and/or neurodegenerative outcome. The neuroprotective actions of neuroactive steroids, together with the sex specific regulation of its levels might provide the basis to design sex-specific neuroprotective therapies. Indeed, some experiments here discussed suggest the viability of this approach.