CB1 receptor selective activation inhibits β-amyloid-induced iNOS protein expression in C6 cells and subsequently blunts tau protein hyperphosphorylation in co-cultured neurons
- 作者：Giuseppe Esposito ; Daniele De Filippis ; Luca Steardo ; Caterina Scuderi ; Claudia Savani ; Vincenzo Cuomo and Teresa Iuvone
- 关键词：Alzheimer's disease ; Tau protein hyperphosphorylation ; Nitric oxide (NO) ; Cannabinoids ; CB1 receptors
- 刊名：Neuroscience Letters
- 出版年：2006
- 期刊代码：52_03043940
- 类别：neu
- 出版时间：1 September 2006
- 卷：404
- 期：3
- 页码：342-346
- 文件大小：222 K
摘要
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.