Progress in Neurobiology
Volume 113, February 2014, Pages 1–5 Special Issue
Allopregnanolone: State of the art [link]
Roberto Cosimo Melcangi a
Gian Carlo Panzica b,c
a Department of Pharmacological and Biomolecular Sciences, Section of Biomedicine and Endocrinology,
Center of Excellence on Neurodegenerative Diseases, Università degli Studi di Milano
b Department of Neuroscience, Università degli Studi di Torino
c Neuroscience Institute Cavalieri Ottolenghi (NICO)
Allopregnanolone, a neuroactive steroid derived from progesterone, is synthesized within the nervous tissue, by means of specific enzymes. Contrary to progesterone and its first metabolite dihydroprogesterone, allopregnanolone is able to interact with GABA-A receptor and not with the classical progesterone receptor. This suggests that the effect of progesterone administration may be due to activation of progesterone receptor, or of GABA-A receptor, or both. However, this is rarely considered in the experimental studies.
Here we summarize and discuss the hot topics involving the actions of allopregnanolone within the nervous tissue. One major role of this neuroactive steroid is neuroprotection in case of lesion, ischemia or peripheral neuropathies (i.e., diabetes). In addition, allopregnanolone may reduce the symptoms of neurodegenerative diseases (e.g., Alzheimer, Parkinson, Niemann–Pick type C, multiple sclerosis) in animal models and now translational studies are developed for its therapeutic use. Allopregnanolone may exert a beneficial effect also in case of neuropathic pain and it is also a potential candidate for the treatment of mood and anxiety disorders.
Finally, this neuroactive steroid seems to have important physiological roles in the early differentiation of some neural circuits (in particular at hippocampal level), and to reduce stress during pregnancy. In conclusion, it appears that allopregnanolone is a key regulator of physiological functions and may have interesting therapeutic perspectives for neurodegenerative and psychiatric disorders.
Since 2001, this meeting represented an important event for basic and clinical researchers working on this emerging scientific topic. We will address state-of-the-art approaches in the field of steroids and nervous system, including behavior, epigenetics, genomic and non-genomic actions, the vitamin D, neurodegenerative and psychiatric disorders, and the interference among endocrine disruptors and steroid signaling.
L’inibizione della proteina JNK rallenta la progressione della malattia che colpisce i motoneuroni ed è la prima causa genetica di morte nell’infanzia. Lo dimostra uno studio pubblicato su Frontiers in Molecular Neuroscience dal nostro gruppo di ricerca guidato da Alessandro Vercelli, in collaborazione con l’Istituto Mario Negri di Milano. Chiarire i meccanismi molecolari alla base della SMA può aprire la strada allo sviluppo di nuove terapie.