Department of Biochemistry, University of Padova, Italy.
Biofactors. 2011 May-Jun;37(3):189-96. doi: 10.1002/biof.157.
More than one century ago "a peculiar disorder of the cerebral cortex" was noticed in a middle-aged patient who had been affected by dementia in the last years of his life. The postmortem hallmarks of his brain were protein plaques, neurofibrillary tangles, and atherosclerotic changes: the neuropathologist who found these alterations and gave his name to the disease that underlied them was Alois Alzheimer (Alzheimer et al., Clin Anat 1995;8:429-431). Following its discovery, the disease has been studied with a vigor that went parallel to the increase of its social importance. The amount of information amassed in the literature is impressive, but knowledge on the mechanism underlying its onset and its progression is still very limited. Numerous hypotheses on the molecular pathogenesis of the Alzheimer's disease (AD) have been proposed and two have gradually gained wide consensus: (i) the amyloid cascade hypothesis, first proposed on the basis of the toxicity evoked by the deposition of amyloid β (Aβ) aggregates; (ii) the Ca(2+) hypothesis, which focuses on the correlation between the dysfunction of Ca(2+) homeostasis and the neurodegeneration process. This succinct review will discuss the essential aspects of the role of Ca(2+) homeostasis dysregulation in the onset and development of AD.
一个多世纪以前，一位中年患者在生命的最后几年中出现了痴呆症，人们注意到他的大脑皮层存在一种“特殊的紊乱”。他大脑的死后特征是蛋白质斑块、神经原纤维缠结和动脉粥样硬化变化：发现这些改变并为其命名的神经病理学家是 Alois Alzheimer（Alzheimer 等人，临床解剖学 1995 年；8:429-431）。自发现以来，人们以与该病社会重要性增加并行的力度对其进行了研究。文献中积累的信息量令人印象深刻，但对其发病机制和进展的了解仍然非常有限。已经提出了许多关于阿尔茨海默病（AD）分子发病机制的假说，其中两个假说逐渐得到广泛共识：（i）淀粉样蛋白级联假说，最初是基于淀粉样蛋白β（Aβ）聚集体沉积引起的毒性而提出的；（ii）Ca(2+)假说，该假说集中于 Ca(2+)动态平衡功能障碍与神经退行性过程之间的相关性。这篇简洁的综述将讨论 Ca(2+)动态平衡失调在 AD 发病和发展中的关键作用。
