Neuroactive Steroids and Peripheral Neuropathy

Abstract

Peripheral neuropathy, either inherited or acquired, is a very common disorder for which effective clinical treatments are not yet available. Neuroactive steroids such as progesterone, testosterone, and their reduced metabolites represent a promising therapeutic option for peripheral neuropathy. Peripheral nerves are able to synthesize and metabolize neuroactive steroids and are a target for these molecules since they express classical and nonclassical steroid receptors. Neuroactive steroids modulate the expression of key transcription factors (TFs) for Schwann cell function, regulate Schwann cell proliferation, and promote the expression of myelin proteins. Interestingly, they are also able to counteract biochemical, morphological, and functional alterations of peripheral nerves in different experimental models of neuropathy, including the alterations caused by aging, diabetic neuropathy, and physical injury. Therefore, neuroactive steroids and pharmacological agents that are able to increase their local synthesis and the synthetic ligands for their receptors offer a promising potential for the treatment of different forms of peripheral neuropathy.