کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4350472 1296986 2006 5 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
CB1 receptor selective activation inhibits β-amyloid-induced iNOS protein expression in C6 cells and subsequently blunts tau protein hyperphosphorylation in co-cultured neurons
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
CB1 receptor selective activation inhibits β-amyloid-induced iNOS protein expression in C6 cells and subsequently blunts tau protein hyperphosphorylation in co-cultured neurons
چکیده انگلیسی

Among the wide range of neuro-inflammatory signalling molecules released by β-amyloid-stimulated astroglial cells, nitric oxide (NO) plays a fundamental role in AD aethiopathogenesis since it directly promotes neuronal tau protein hyperphosphorylation leading to neurofibrillary tangle formation. Synthetic cannabinoids (CBs), via a selective CB1 receptor activation, negatively modulates both iNOS protein expression and NO production induced by pro-inflammatory stimuli. In this study we investigated the role of both the non-selective WIN 55,212-2 and the selective CB1 receptor agonist, ACEA, on: (i) NO production, (ii) iNOS protein expression in (1–42) β-amyloid peptide (Aβ)-stimulated C6 rat glioma cells and (iii) tau protein hyperphosphorylation in co-cultured differentiated PC12 neurons. Our results demonstrated that synthetic CBs, by a selective CB1 effect, down-regulate iNOS protein expression and NO production in Aβ-stimulated C6 cells. This effect leads, in turn, to a significant and concentration-dependent inhibition of NO-dependent tau protein hyperphosphorylation in co-cultured PC12 neurons. The results of the present study extend our knowledge about the neuroprotective actions of synthetic CBs on Aβ-dependent neurotoxicity in vitro. Furthermore, our study allows us to identify, in the CB1-mediated inhibition of astroglial-derived NO, a new potential target to blunt tau hyperphosphorylation and the consequent related tauopathy in AD.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 404, Issue 3, 1 September 2006, Pages 342–346
نویسندگان
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