Substantial evidence supports that progesterone exerts many functions in the central and peripheral nervous
system unrelated to its classical role in reproduction. In this review we first discussed progesterone effects following
binding to the classical intracellular progesterone receptors A and B and several forms of membrane progesterone
receptors, the modulation of intracellular signalling cascades and the interaction of progesterone reduced metabolites with
neurotransmitter receptors. We next described our results involving animal models of human neuropathologies to
elucidate the protective roles of progesterone. We described: (a) the protective and promyelinating effects of progesterone
in experimental spinal cord injury; (b) the progesterone protective effects exerted upon motoneurons in the degenerating
spinal cord of Wobbler mouse model of amyotropic lateral sclerosis; (c) the protective and anti-inflammatory effects of
progesterone in the murine experimental autoimmune encephalomyelitis model of multiple sclerosis and after lysolecithin
demyelination; (d) the progesterone prevention of nociception and neuropathic pain which follow spinal cord injury; and
(e) the protective effect of progesterone in experimental ischemic stroke. Whenever available, the molecular mechanisms
involved in these progesterone effects were examined. The multiplicity of progesterone beneficial effects has opened new
venues of research for neurological disorders. In this way, results obtained in animal models could provide the basis for
novel therapeutic strategies and pre-clinical studies.
Keywords: Progesterone, neuroprotection, steroid receptors, animal models.
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