Metcalfe Maria Jose, Figueiredo-Pereira Maria E
Department of Biological Sciences, Hunter College, City University of New York, New York, NY, USA.
Mt Sinai J Med. 2010 Jan-Feb;77(1):50-8. doi: 10.1002/msj.20163.
Alzheimer's disease is a chronic, age-related neurodegenerative disorder. Neurofibrillary tangles are among the pathological hallmarks of Alzheimer's disease. Neurofibrillary tangles consist of abnormal protein fibers known as paired helical filaments. The accumulation of paired helical filaments is one of the most characteristic cellular changes in Alzheimer's disease. Tau protein, a microtubule-associated protein, is the major component of paired helical filaments. Tau in paired helical filaments is hyperphosphorylated, truncated, and aggregated. What triggers the formation of paired helical filaments is not known, but neuroinflammation could play a role. Neuroinflammation is an active process detectable in the earliest stages of Alzheimer's disease. The neuronal toxicity associated with inflammation makes it a potential risk factor in the pathogenesis of Alzheimer's disease. Determining the sequence of events that lead to this devastating disease has become one of the most important goals for the prevention and treatment of Alzheimer's disease. In this review, we focus on the pathological properties of tau thought to play a role in neurofibrillary tangle formation and summarize how central nervous system inflammation might be a critical contributor to the pathology of Alzheimer's disease. A better understanding of the mechanisms that cause neurofibrillary tangle formation is of clinical importance for developing therapeutic strategies to prevent and treat Alzheimer's disease. One of the major challenges facing us is singling out neuroinflammation as a therapeutic target for the prevention of Alzheimer's disease neurodegeneration. The challenge is developing therapeutic strategies that prevent neurotoxicity linked to inflammation without compromising its neuroprotective role.
阿尔茨海默病是一种与年龄相关的慢性神经退行性疾病。神经原纤维缠结是阿尔茨海默病的病理特征之一。神经原纤维缠结由称为双螺旋丝的异常蛋白质纤维组成。双螺旋丝的积累是阿尔茨海默病最具特征性的细胞变化之一。tau蛋白是一种微管相关蛋白，是双螺旋丝的主要成分。双螺旋丝中的tau蛋白发生了过度磷酸化、截短和聚集。引发双螺旋丝形成的原因尚不清楚，但神经炎症可能起了作用。神经炎症是在阿尔茨海默病最早阶段就可检测到的一个活跃过程。与炎症相关的神经元毒性使其成为阿尔茨海默病发病机制中的一个潜在危险因素。确定导致这种毁灭性疾病的事件顺序已成为预防和治疗阿尔茨海默病最重要的目标之一。在本综述中，我们重点关注tau蛋白在神经原纤维缠结形成中可能发挥作用的病理特性，并总结中枢神经系统炎症如何可能是阿尔茨海默病病理的关键促成因素。更好地理解导致神经原纤维缠结形成的机制对于制定预防和治疗阿尔茨海默病的治疗策略具有临床重要性。我们面临的主要挑战之一是将神经炎症作为预防阿尔茨海默病神经退行性变治疗靶点单独挑出。挑战在于开发既能预防与炎症相关的神经毒性又不损害其神经保护作用的治疗策略。
