| Autor: |
Nuzzo MT; Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, 00146, Rome, Italy., Fiocchetti M; Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, 00146, Rome, Italy., Totta P; Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, 00146, Rome, Italy., Melone MAB; Department of Medical, Surgical, Neurological, Metabolic, and Ageing Sciences, University of Campania Luigi Vanvitelli, Naples, Italy.; Institute of Biosciences and Bioresources (IBBR-CNR), Naples, Italy., Cardinale A; Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, 00146, Rome, Italy.; S. Lucia Foundation Hospital IRCCS, Laboratory of Neuroanatomy, Rome, Italy., Fusco FR; S. Lucia Foundation Hospital IRCCS, Laboratory of Neuroanatomy, Rome, Italy., Gustincich S; Area of Neuroscience, International School for Advanced Studies (SISSA), Trieste, Italy.; Department of Neuroscience and Brain Technologies, Italian Institute of Technologies (IIT), Genoa, Italy., Persichetti F; Department of Health Science, University of Eastern Piedmont, Novara, Italy., Ascenzi P; Institute of Biosciences and Bioresources (IBBR-CNR), Naples, Italy.; Interdepartmental Laboratory for Electron Microscopy, Roma Tre University, Via della Vasca Navale 79, 00146, Rome, Italy., Marino M; Department of Science, Roma Tre University, Viale Guglielmo Marconi 446, 00146, Rome, Italy. maria.marino@uniroma3.it.; Institute of Biosciences and Bioresources (IBBR-CNR), Naples, Italy. maria.marino@uniroma3.it. |
| Abstrakt: |
Among several mechanisms underlying the well-known trophic and protective effects of 17β-estradiol (E2) in the brain, we recently reported that E2 induces the up-regulation of two anti-apoptotic and neuroprotectant proteins: huntingtin (HTT) and neuroglobin (NGB). Here, we investigate the role of this up-regulation. The obtained results indicate that E2 promotes NGB-HTT association, induces the localization of the complex at the mitochondria, and protects SK-N-BE neuroblastoma cells and murine striatal cells, which express wild-type HTT (i.e., polyQ 7 ), against H 2 O 2 -induced apoptosis. All E2 effects were completely abolished in HTT-knocked out SK-N-BE cells and in striatal neurons expressing the mutated form of HTT (mHTT; i.e., polyQ 111 ) typical of Huntington's disease (HD). As a whole, these data provide a new function of wild-type HTT which drives E2-induced NGB in mitochondria modulating NGB anti-apoptotic activity. This new function is lost by HTT polyQ pathological expansion. These data evidence the existence of a novel E2/HTT/NGB neuroprotective axis that may play a relevant role in the development of HD therapeutics. |
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