Institute of Neuroimmunology, 84510 Bratislava, Slovak Republic.
J Neuroinflammation. 2012 Mar 7;9:47. doi: 10.1186/1742-2094-9-47.
Neurodegeneration, induced by misfolded tau protein, and neuroinflammation, driven by glial cells, represent the salient features of Alzheimer's disease (AD) and related human tauopathies. While tau neurodegeneration significantly correlates with disease progression, brain inflammation seems to be an important factor in regulating the resistance or susceptibility to AD neurodegeneration. Previously, it has been shown that there is a reciprocal relationship between the local inflammatory response and neurofibrillary lesions. Numerous independent studies have reported that inflammatory responses may contribute to the development of tau pathology and thus accelerate the course of disease. It has been shown that various cytokines can significantly affect the functional and structural properties of intracellular tau. Notwithstanding, anti-inflammatory approaches have not unequivocally demonstrated that inhibition of the brain immune response can lead to reduction of neurofibrillary lesions. On the other hand, our recent data show that misfolded tau could represent a trigger for microglial activation, suggesting the dual role of misfolded tau in the Alzheimer's disease inflammatory cascade. On the basis of current knowledge, we can conclude that misfolded tau is located at the crossroad of the neurodegenerative and neuroinflammatory pathways. Thus disease-modified tau represents an important target for potential therapeutic strategies for patients with Alzheimer's disease.
神经退行性变，由错误折叠的 tau 蛋白诱导，神经炎症，由神经胶质细胞驱动，代表了阿尔茨海默病 (AD) 和相关人类 tau 病的显著特征。虽然 tau 神经退行性变与疾病进展显著相关，但脑炎症似乎是调节 AD 神经退行性变抵抗或易感性的重要因素。以前已经表明，局部炎症反应与神经纤维缠结病变之间存在相互关系。许多独立的研究报告表明，炎症反应可能有助于 tau 病理学的发展，从而加速疾病进程。已经表明，各种细胞因子可以显著影响细胞内 tau 的功能和结构特性。尽管如此，抗炎方法并没有明确表明抑制大脑免疫反应可以导致神经纤维缠结病变减少。另一方面，我们最近的数据表明，错误折叠的 tau 可能代表小胶质细胞激活的触发因素，这表明错误折叠的 tau 在阿尔茨海默病炎症级联反应中具有双重作用。基于目前的知识，我们可以得出结论，错误折叠的 tau 位于神经退行性变和神经炎症途径的十字路口。因此，疾病修饰的 tau 是阿尔茨海默病患者潜在治疗策略的重要靶点。
