Ca^(2+)失调与阿尔茨海默病发生发展关系的研究进展

Progress of the relationship between Ca^(2+) dysregulation and Alzheimer's disease development

阿尔茨海默病(Alzheimer’s disease,AD)是全球老年人中最常见的神经退行性疾病。在对家族性AD的动物模型和个别AD患者死后脑组织的研究中发现,除了Aβ42水平升高外,神经元内Ca2+信号失调,并且Ca2+信号蛋白表达水平也发生了改变。淀粉样蛋白斑、神经元纤维缠结和神经元丢失是AD的后期标志,它们的共同点可能是破坏神经元钙离子信号。细胞内钙离子水平提高在功能上与淀粉样蛋白斑、早老素突变、tau缠结和突触功能障碍相关,基于这些研究,产生了AD的Ca2+假说。主要介绍神经元内Ca2+失调与AD的关系以及钙拮抗剂作为AD的潜在治疗方法。

Alzheimer＇s disease （AD） is the most common neurodegenerative disorder among the aged in the world. In addition to the increase in Al342 levels, disturbances in neuronal calcium（Ca2＋） signaling and alterations in expression levels of Ca2＋ signaling proteins have been observed in animal models of familial AD and in studies of postmortem brain samples from sporadic AD patients. Although amyloid plaques, neurofibrillary tangles and neuronal loss are late stage markers of AD, one common element of them is disrupted neuronal calcium signaling. Increased intracellular calcium levels are functionally linked to amyloid plaques, presenilin mutations, tau tangles and synaptic dysfunction. Based on these studies, the Ca2＋ hypothesis of AD has been proposed. In this review, we discuss the relationship between Ca2＋ dysregulation and AD, and Ca2＋ blockers may be potential AD treatments.