Probst-Cousin Stefan, Bergmann Markus, Maihöfner Christian, Neundörfer Bernhard, Heuss Dieter
Centre of Neuromuscular Disorders, Department of Neurology Friedrich-Alexander-University Erlangen-Nuremberg Schwabachanlage 6, D-91054 Erlangen, Germany.
Amyotroph Lateral Scler Other Motor Neuron Disord. 2004 Sep;5(3):180-7. doi: 10.1080/14660820410019323.
Clinically, amyotrophic lateral sclerosis (ALS) usually presents as a pure motor system disorder, whereas oculomotor and sphincter muscle control of the anus and the bladder appear to be spared. Previously, a lacking expression of calcium binding proteins (CBPs) was demonstrated in vulnerable motor neurons in contrast to spared neuronal populations, e.g., the motor neurons of the cranial nerve III (NO) and the Onufrowicz nucleus (ON), suggesting a potential role of CBPs in the selective motoneuronal vulnerability in ALS. The annexins comprise a multigene family of CBPs, constituting a significant amount of total cellular protein and presumably involved in calcium-homeostasis and intracellular calcium-regulated pathways. We immunohistochemically investigated the expression patterns of annexins A1, A2, A4, A5, A6, and A7 in spinal cord and midbrain tissues from 24 ALS patients and 5 age-matched controls to test the hypothesis that annexins also contribute to the selective vulnerability in ALS. There was no difference in the expression patterns of ALS cases and normal controls. Annexin A1 was expressed in ependymal cells and motor neurons. Annexin A2 could be detected in ependymal and endothelial cells and motor neurons. Annexins A4 and A5 were found in both ependymal and glial cells, whereas annexin A6 was strongly expressed in motor neurons. Annexin A7 was totally absent from central nervous system tissue. A contribution of annexins to the selective vulnerability in ALS could not be derived from our results.
临床上，肌萎缩侧索硬化症（ALS）通常表现为单纯的运动系统疾病，而眼动以及肛门和膀胱的括约肌控制似乎未受影响。此前，与未受影响的神经元群体（例如，动眼神经（NO）和奥努夫罗维奇核（ON）的运动神经元）相比，在易损运动神经元中发现钙结合蛋白（CBP）表达缺失，这表明CBP在ALS选择性运动神经元易损性中可能发挥作用。膜联蛋白是CBP的一个多基因家族，占细胞总蛋白的很大一部分，可能参与钙稳态和细胞内钙调节途径。我们采用免疫组织化学方法研究了24例ALS患者和5例年龄匹配对照的脊髓和中脑组织中膜联蛋白A1、A2、A4、A5、A6和A7的表达模式，以检验膜联蛋白也导致ALS选择性易损性的假说。ALS病例和正常对照的表达模式没有差异。膜联蛋白A1在室管膜细胞和运动神经元中表达。膜联蛋白A2可在室管膜细胞、内皮细胞和运动神经元中检测到。膜联蛋白A4和A5在室管膜细胞和神经胶质细胞中均有发现，而膜联蛋白A6在运动神经元中强烈表达。中枢神经系统组织中完全不存在膜联蛋白A7。我们的结果无法得出膜联蛋白对ALS选择性易损性有影响的结论。
