Macchi Beatrice, Marino-Merlo Francesca, Frezza Caterina, Cuzzocrea Salvatore, Mastino Antonio
Department of System Medicine, University of Rome "Tor Vergata", Via Montpellier 1, 00133, Rome, Italy,
Mol Neurobiol. 2014 Oct;50(2):463-72. doi: 10.1007/s12035-014-8641-9. Epub 2014 Jan 21.
Although the central nervous system (CNS) has been defined as a privileged site in Alzheimer's disease (AD), periphery can be more than simply witness of events leading to neurodegeneration. The CNS and peripheral blood can mutually communicate through cells and factors trafficking from the circulation into the brain and vice versa. A number of articles have reviewed inflammatory profiles and programmed cell death (PCD) in AD, separately in the CNS and at the peripheral level. This review does not provide an exhaustive account of what has been published on inflammation and PCD in AD. Rather, the aim of this review is to focus on possible linkages between the central and the peripheral compartments during AD progression, by critically analyzing, in a comparative manner, phenomena occurring in the CNS as well as the peripheral blood. In fact, growing evidence suggests that CNS and peripheral inflammation might present common features in the disease. Microarrays and metabolomics revealed that dysfunction of the glycolytic and oxidative pathways is similar in the brain and in the periphery. Moreover, dysregulated autophagosome/lysosomal molecular machinery, both at the CNS and the peripheral level, in AD-related cell damage, has been observed. Possible implications of these observations have been discussed.
尽管中枢神经系统（CNS）在阿尔茨海默病（AD）中被定义为一个特殊部位，但外周组织不仅仅是导致神经退行性变事件的旁观者。中枢神经系统和外周血可以通过细胞和因子在循环系统与大脑之间的相互运输进行交流。许多文章分别对AD中枢神经系统和外周水平的炎症特征及程序性细胞死亡（PCD）进行了综述。本综述并非对AD中炎症和PCD已发表的内容进行详尽阐述。相反，本综述的目的是通过以比较的方式批判性地分析中枢神经系统和外周血中发生的现象，聚焦于AD进展过程中中枢和外周部分之间可能的联系。事实上，越来越多的证据表明中枢神经系统和外周炎症在该疾病中可能具有共同特征。微阵列和代谢组学研究表明，大脑和外周组织中糖酵解和氧化途径的功能障碍相似。此外，在AD相关细胞损伤中，已观察到中枢神经系统和外周水平的自噬体/溶酶体分子机制失调。这些观察结果的可能影响也已进行了讨论。
