Dewar D, Graham D I, Teasdale G M, McCulloch J
Wellcome Surgical Institute, University of Glasgow, UK.
Dementia. 1994 May-Aug;5(3-4):168-73. doi: 10.1159/000106716.
Excessive stimulation of glutamate receptors and elevation of intracellular calcium levels initiate the neurodegenerative process resulting from cerebral ischemia. However, the subsequent cascade of molecular changes which are of pathogenic significance is less well understood. Breakdown of the cytoskeleton may be involved in the progression from compromise of neuronal viability to irreversible damage. Alteration of the microtubule-associated protein tau, as reflected by increased Alz-50 immunoreactivity, was induced by permanent focal cerebral ischemia in vivo but only in a proportion of neurones. Alz-50 immunoreactive neurones did not exhibit the characteristics of irreversible ischemic cell damage. Increased immunoreactivity to the stress response protein ubiquitin was also induced by ischemia in a proportion of neurones. Both proteins are components of neurofibrillary tangles in Alzheimer's disease. Alterations of the microtubule-associated protein tau may be a feature of the early stages of the ischemia-induced degeneration and the ubiquitin response may be an attempt by compromised neurones to deal with the presence of abnormal proteins.
谷氨酸受体的过度刺激和细胞内钙水平的升高引发了由脑缺血导致的神经退行性过程。然而，随后具有致病意义的分子变化级联却不太为人所了解。细胞骨架的破坏可能参与了从神经元活力受损到不可逆损伤的进展过程。体内永久性局灶性脑缺血可诱导微管相关蛋白tau的改变，这通过Alz - 50免疫反应性增加得以体现，但仅在一部分神经元中出现。Alz - 50免疫反应性神经元并未表现出不可逆缺血性细胞损伤的特征。缺血还在一部分神经元中诱导了对应激反应蛋白泛素的免疫反应性增加。这两种蛋白都是阿尔茨海默病神经原纤维缠结的组成成分。微管相关蛋白tau的改变可能是缺血诱导性变性早期阶段的一个特征，而泛素反应可能是受损神经元应对异常蛋白存在的一种尝试。
