Savory John, Herman Mary M, Ghribi Othman
Department of Pathology, University of Virginia, Charlottesville, VA, USA.
J Alzheimers Dis. 2006 Nov;10(2-3):135-44. doi: 10.3233/jad-2006-102-302.
For four decades the controversial question concerning a possible role for aluminum neurotoxicity in contributing to the pathogenesis of Alzheimer's disease has been debated, and studies by different investigators have yielded contradictory results. The lack of sensitivity to aluminum neurotoxicity in transgenic mouse models of Alzheimer's disease has not allowed the system to be used to explore important aspects of this toxicity. Rabbits are particularly sensitive to aluminum neurotoxicity and they develop severe neurological changes that are dependent on dose, age and route of administration. The most prominent feature induced by aluminum in rabbit brain is a neurofibrillary degeneration that shares some similarity with the neurofibrillary tangles found in Alzheimer's disease patients. In the present review we discuss data from our laboratory and others, on the effects of aluminum on behaviour, neurologic function and morphology, using aluminum administered to rabbits via different routes. Finally, we will examine data on the possible cellular mechanisms underlying aluminum neurotoxicity, and potential neuroprotective strategies against aluminum toxicity.
四十年来，关于铝神经毒性在阿尔茨海默病发病机制中可能发挥的作用这一有争议的问题一直存在争论，不同研究者的研究得出了相互矛盾的结果。阿尔茨海默病转基因小鼠模型对铝神经毒性缺乏敏感性，这使得该系统无法用于探索这种毒性的重要方面。兔子对铝神经毒性特别敏感，它们会出现严重的神经变化，这些变化取决于剂量、年龄和给药途径。铝在兔脑中引起的最显著特征是神经原纤维变性，这与阿尔茨海默病患者脑中发现的神经原纤维缠结有一些相似之处。在本综述中，我们讨论了来自我们实验室和其他实验室的数据，这些数据涉及通过不同途径给兔子施用铝后，铝对行为、神经功能和形态的影响。最后，我们将研究关于铝神经毒性潜在细胞机制的数据，以及针对铝毒性的潜在神经保护策略。
