Neuroactive steroids and peripheral neuropathy

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Brain Res Rev. 2007 May 6

Neuroactive steroids and peripheral neuropathy.

Roglio I, Giatti S, Pesaresi M, Bianchi R, Cavaletti G, Lauria G,

R-Segura LM, Melcangi RC.

Department of Endocrinology and Center of Excellence on

Neurodegenerative Diseases, University of Milan, Via Balzaretti 9,

20133, Milan, Italy.

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.