دورية أكاديمية
Early defect of transforming growth factor β1 formation in Huntington's disease.
العنوان: | Early defect of transforming growth factor β1 formation in Huntington's disease. |
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المؤلفون: | BATTAGLIA, Giuseppe, BRUNO, Valeria Maria Gloria, FRATI, Luigi, NICOLETTI, Ferdinando, SQUITIERI, Ferdinando, Milena Cannella, Barbara Riozzi, Sara Orobello, Marion L. Maat Schieman, Eleonora Aronica, Carla Letizia Busceti, Andrea Ciarmiello, Silvia Alberti, Enrico Amico, Jenny Sassone, Simonetta Sipione |
المساهمون: | Battaglia, Giuseppe, Milena, Cannella, Barbara, Riozzi, Sara, Orobello, Marion L., Maat Schieman, Eleonora, Aronica, Carla Letizia, Busceti, Andrea, Ciarmiello, Silvia, Alberti, Enrico, Amico, Jenny, Sassone, Simonetta, Sipione, Bruno, Valeria Maria Gloria, Frati, Luigi, Nicoletti, Ferdinando, Squitieri, Ferdinando |
بيانات النشر: | WILEY-BLACKWELL |
سنة النشر: | 2011 |
المجموعة: | Sapienza Università di Roma: CINECA IRIS |
مصطلحات موضوعية: | ransforming growth factor-beta, brain cortex, transforming growth factor-β, huntington's disease, neurodegeneration, neurodysfunction, peripheral marker, transforming growth factor-beta |
الوصف: | A defective expression or activity of neurotrophic factors, such as brain- and glial-derived neurotrophic factors, contributes to neuronal damage in Huntington's disease (HD). Here, we focused on transforming growth factor-beta (TGF-beta(1)), a pleiotropic cytokine with an established role in mechanisms of neuroprotection. Asymptomatic HD patients showed a reduction in TGF-beta(1) levels in the peripheral blood, which was related to trinucleotide mutation length and glucose hypometabolism in the caudate nucleus. Immunohistochemical analysis in post-mortem brain tissues showed that TGF-beta(1) was reduced in cortical neurons of asymptomatic and symptomatic HD patients. Both YAC128 and R6/2 HD mutant mice showed a reduced expression of TGF-beta(1) in the cerebral cortex, localized in neurons, but not in astrocytes. We examined the pharmacological regulation of TGF-beta(1) formation in asymptomatic R6/2 mice, where blood TGF-beta(1) levels were also reduced. In these R6/2 mice, both the mGlu2/3 metabotropic glutamate receptor agonist, LY379268, and riluzole failed to increase TGF-beta(1) formation in the cerebral cortex and corpus striatum, suggesting that a defect in the regulation of TGF-beta(1) production is associated with HD. Accordingly, reduced TGF-beta(1) mRNA and protein levels were found in cultured astrocytes transfected with mutated exon 1 of the human huntingtin gene, and in striatal knock-in cell lines expressing full-length huntingtin with an expanded glutamine repeat. Taken together, our data suggest that serum TGF-beta(1) levels are potential biomarkers of HD development during the asymptomatic phase of the disease, and raise the possibility that strategies aimed at rescuing TGF-beta(1) levels in the brain may influence the progression of HD. |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
العلاقة: | info:eu-repo/semantics/altIdentifier/pmid/20082658; info:eu-repo/semantics/altIdentifier/wos/WOS:000288798000010; volume:15; issue:3; firstpage:555; lastpage:571; numberofpages:17; journal:JOURNAL OF CELLULAR AND MOLECULAR MEDICINE; http://hdl.handle.net/11573/376481Test; info:eu-repo/semantics/altIdentifier/scopus/2-s2.0-79953298589; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000288798000010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=0c7ff228ccbaaa74236f48834a34396aTest; http://www.scopus.com/inward/record.url?eid=2-s2.0-79953298589&partnerID=65&md5=c888b2ee901c0023fd11e112f022eb90Test |
DOI: | 10.1111/j.1582-4934.2010.01011.x |
الإتاحة: | https://doi.org/10.1111/j.1582-4934.2010.01011.xTest http://hdl.handle.net/11573/376481Test http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=000288798000010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=0c7ff228ccbaaa74236f48834a34396aTest http://www.scopus.com/inward/record.url?eid=2-s2.0-79953298589&partnerID=65&md5=c888b2ee901c0023fd11e112f022eb90Test |
رقم الانضمام: | edsbas.3602C72F |
قاعدة البيانات: | BASE |
DOI: | 10.1111/j.1582-4934.2010.01011.x |
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