CONICET | Buscador de Institutos y Recursos Humanos

Central nervous system (CNS) injuries and neurodegenerative diseases show a broadspectrum of common pathophysiological processes, including oxidative stress, neuroinflammation,excitotoxicity, demyelination and neurotransmission dysfunctions. Over the pastdecades, valuable experimental investigations have helped to clarify the roleand timing of these multiple molecular and cellular mechanisms in each of theseparticular disorders, which usually overlap and critically contribute tolong-term disability. However, up to now, no definite cures or effective disease-modifyingtherapies are available for any of these conditions. This has led to an active searchof novel therapeutic approaches, including the repositioning of existing drugs for new indications, as a valid approach to promptly move candidate molecules toclinical trials. Progesterone, asteroid with a crucial role in the reproductive function in mammals, stands as one of these promising repositioningmolecules to modulate the complex array of cellular and molecular eventsobserved in several of these central nervous system diseases (Stein and Sayeed, 2019). Indeed, a great number of preclinicalstudies have provided solid basis for supporting a protective effect of progesterone in stroke, traumatic brain injury, spinal cord trauma, central andperipheral neuropathies, multiple sclerosis, and Alzheimer and Parkinson disease (for a review, (González et al., 2018) (Gonzalez et al., 2019) Notwithstanding thisremarkable number of studies exploring the beneficial effects of progesterone in CNS disorders, few of them offer a deeper look at the different receptors and complex signaling cascades involved. This perspective aims at expanding ourview on the variety of receptors and signaling pathways that might be involved in progesterone-mediated actions in the nervous system as part of a rational strategy to promote a successful translation of steroid-based therapies for the treatment of neurological diseases.