Biessels G, Gispen W H
Rudolf Magnus Institute for Neurosciences, Department of Medical Pharmacology, Utrecht, NL.
Life Sci. 1996;59(5-6):379-87. doi: 10.1016/0024-3205(96)00316-5.
In this paper we discuss the possible role of disturbed neuronal calcium homeostasis in brain aging and diabetic neuropathy. Disturbances in the homeostasis of cytosolic calcium concentration have been implicated in the pathogenesis of various acute and chronic neurodegenerative disorders and in brain aging. Obviously, these disorders do not all share the same pathogenetic mechanisms. However, a number of the pathogenetic mechanisms involved have in common that they may ultimately cause loss of calcium homeostasis, leading to neuronal damage. By identifying the possible role of calcium, treatment strategies can be developed that may be effective in a variety of neurodegenerative disorders, despite differences in their pathogenesis. Our aim is to explore some of the similarities that exist between a number of processes that have been implicated in the pathogenesis of brain aging and diabetic neuropathy, including ischemia, oxidative stress and non-enzymatic protein glycosylation. Each of these factors might impair neuronal calcium homeostasis, and ultimately lead to neurodegenerative changes. By discussing the putative role of these specific factors in two apparently dissimilar disorders, such as brain aging and diabetic neuropathy, we obviously do not intend to suggest that their pathogenesis is one and the same. Instead, by examining the relative role of these factors in two different types of neurodegenerative disorders we would like to emphasize the importance of disturbances in cellular calcium homeostasis as a final common pathway in neuronal damage resulting from various noxious events.
在本文中，我们探讨了神经元钙稳态紊乱在脑衰老和糖尿病性神经病变中可能发挥的作用。胞浆钙浓度稳态的紊乱与各种急性和慢性神经退行性疾病的发病机制以及脑衰老有关。显然，这些疾病并非都具有相同的致病机制。然而，所涉及的一些致病机制的共同点在于，它们最终可能导致钙稳态丧失，进而引起神经元损伤。通过确定钙的可能作用，可以制定出在各种神经退行性疾病中可能有效的治疗策略，尽管它们的发病机制存在差异。我们的目的是探讨一些与脑衰老和糖尿病性神经病变发病机制相关的过程之间存在的相似性，包括缺血、氧化应激和非酶蛋白糖基化。这些因素中的每一个都可能损害神经元钙稳态，并最终导致神经退行性改变。通过讨论这些特定因素在两种明显不同的疾病（如脑衰老和糖尿病性神经病变）中的假定作用，我们显然并非意在表明它们的发病机制是相同的。相反，通过研究这些因素在两种不同类型的神经退行性疾病中的相对作用，我们希望强调细胞钙稳态紊乱作为各种有害事件导致神经元损伤的最终共同途径的重要性。
