Neuroactive steroids and peripheral neuropathy.
Peripheral neuropathy, either inherited or acquired, represents a very common disorder for which effective clinical treatments are not available yet. Observations here summarized indicate that neuroactive steroids, such as progesterone, testosterone and their reduced metabolites, might represent a promising therapeutic option. Peripheral nerves are able to synthesize and metabolize neuroactive steroids and are a target for these molecules, since they express classical and non-classical steroid receptors. Neuroactive steroids modulate the expression of key transcription factors for Schwann cell function, regulate Schwann cell proliferation and promote the expression of myelin proteins involved in the maintenance of myelin multilamellar structure, such as myelin protein zero and peripheral myelin protein 22. These actions may result in the protection and regeneration of peripheral nerves affected by different forms of pathological alterations. Indeed, neuroactive steroids are 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, pharmacological agents able to increase their local synthesis and synthetic ligands for their receptors have a promising potential for the treatment of different forms of peripheral neuropathy.
Roglio
Ilaria
I
Department of Endocrinology and Center of Excellence on Neurodegenerative Diseases, University of Milan, Via Balzaretti 9, 20133, Milan, Italy.
Giatti
Silvia
S
Pesaresi
Marzia
M
Bianchi
Roberto
R
Cavaletti
Guido
G
Lauria
Giuseppe
G
Garcia-Segura
Luis-Miguel
LM
Melcangi
Roberto Cosimo
RC
D000818:Animals; D006801:Humans; D010525:Peripheral Nerves / Q000187:drug effects / Q000378:metabolism*; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D012583:Schwann Cells / Q000187:drug effects / Q000378:metabolism; D013256:Steroids / Q000378:metabolism* / Q000494:pharmacology
D013256:Steroids