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进行性记忆障碍、与局部炎症相关的β-淀粉样蛋白(β-amyloid,Aβ)斑块、神经原纤维缠结和选择性脑区神经元脱失是Alzheimer病(Alzheimer’s disease,AD)的特征。虽然β-淀粉样前体蛋白(β-amyloid precursor protein,APP)和Aβ在AD的病因学中起关键作用,但究竟何种形式的APP或Aβ与AD脑内的神经元易损性有关仍不清楚。最近已经公认,作为老年人痴呆的另一种病因,脑缺血促进了AD的发病,而认知功能严重减退的患者和潜在的AD患者发生脑缺血事件的风险增高。此外,载脂蛋白E(apolipoprotein E,ApoE)ε4等位基因既是AD的危险因素,也是脑缺血和脑出血后转归不良的危险因素。最近已经报道了AD模型中降低神经元死亡阈值的一些因素和分子机制,在这些神经炎症中似乎起着重要的作用。在中枢神经系统中,AD神经病理学和缺血性损伤的发展和成熟均以神经胶质细胞活化和炎症介质上调为特征。业已证实,抗炎症策略对体内AD样神经病理学和缺血性损伤的预防和治疗的确有益。本文对提示人APP在神经元的过度表达促使脑更易遭受缺血性损伤的一些研究结果进行了总结,并对增强神经元对缺血性卒中易感性的一些因素做了介绍。
Progressive memory impairment, loss of beta-amyloid (Aβ) plaques associated with local inflammation, neurofibrillary tangles and selective brain regions are characteristic of Alzheimer’s disease (AD) . Although beta-amyloid precursor protein (APP) and Aβ play key roles in the aetiology of AD, what form of APP or Aβ is associated with neuronal vulnerability in AD brain Not clear. It has recently been recognized that as another cause of dementia in the elderly, cerebral ischemia contributes to the onset of AD, while patients with impaired cognition and potentially AD have a higher risk of developing cerebral ischemic events. In addition, apolipoprotein E (ApoE) ε4 allele is not only a risk factor for AD, but also a risk factor for poor outcome after cerebral ischemia and cerebral hemorrhage. It has recently been reported that some of the factors and molecular mechanisms that reduce the threshold of neuronal death in AD models appear to play an important role in these neuroinflammation. In the central nervous system, development and maturation of AD neuropathology and ischemic injury are characterized by activation of glial cells and upregulation of inflammatory mediators. It has been demonstrated that anti-inflammatory strategies are indeed beneficial in the prevention and treatment of AD-like neuropathology and ischemic injury in vivo. This article summarizes some of the findings that suggest that overexpression of APP in neurons contributes to ischemic injury in the brain and describes some of the factors that enhance neuronal susceptibility to ischemic stroke.