THE ROLE OF CALCIUM-BINDING PROTEINS IN SELECTIVE MOTONEURON VULNERABILITY IN AMYOTROPHIC-LATERAL-SCLEROSIS
THE ROLE OF CALCIUM-BINDING PROTEINS IN SELECTIVE MOTONEURON VULNERABILITY IN AMYOTROPHIC-LATERAL-SCLEROSIS
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DOI：
10.1002/ana.410360608
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发表时间：
1994-12-01
影响因子：
11.2
通讯作者：
APPEL, SH
中科院分区：
文献类型：
--
作者：
ALEXIANU, ME;HO, BK;APPEL, SH
导致肌萎缩侧索硬化症（ALS）中选择性运动神经元丢失的因素仍不明确。为了研究钙结合蛋白是否有助于ALS中选择性运动神经元的脆弱性，我们比较了钙结合蛋白-D-28 K和小白蛋白在人类ALS运动神经元群体中的免疫反应性，并在腹侧脊髓杂交细胞系中选择性地容易受到ALS IgG的细胞毒性作用。在人类尸检标本中，免疫反应性钙结合蛋白-D-28 K和小清蛋白在ALS早期丢失的运动神经元群体中不存在（即，皮质和脊髓运动神经元，下颅神经运动神经元），而运动神经元在疾病中晚期或不频繁受损（即，Onuf核运动神经元、眼神经、三叉神经和外展神经神经元）表达的免疫反应性钙结合蛋白-D-28 K和/或小清蛋白水平明显较高。运动神经元-神经母细胞瘤VSC 4.1杂交细胞在二丁酰环AMP诱导分化后失去免疫反应性钙结合蛋白-D-28 K和小清蛋白，并被ALS患者的IgG杀死。未分化的钙结合蛋白/小清蛋白反应性VSC 4.1细胞未被杀死，表达高水平钙结合蛋白-D-28 K和小清蛋白免疫反应性的其他细胞系（黑质-神经母细胞瘤杂交细胞和N18 TG 2神经母细胞瘤亲本细胞）也未被杀死。这些研究表明，降低钙结合蛋白-D-28 K和小清蛋白免疫反应性可能有助于解释ALS运动神经元的选择性脆弱性。
The factors contributing to selective motoneuron loss in amyotrophic lateral sclerosis (ALS) remain undefined. To investigate whether calcium-binding proteins contribute to selective motoneuron vulnerability in ALS, we compared calbindin-D-28K and parvalbumin immunoreactivity in motoneuron populations in human ALS, and in a ventral spinal cord hybrid cell line selectively vulnerable to the cytotoxic effects of ALS IgG. In human autopsy specimens, immunoreactive calbindin-D-28K and parvalbumin were absent in motoneuron populations lost early in ALS (i.e., cortical and spinal motoneurons, lower cranial nerve motoneurons), while motoneurons damaged late or infrequently in the disease (i.e., Onuf's nucleus motoneurons, oculomotor, trochlear, and abducens nerve neurons) expressed markedly higher levels of immunoreactive calbindin-D-28K and/or parvalbumin. Motoneuron-neuroblastoma VSC 4.1 hybrid cells lost immunoreactive calbindin-D-28K and parvalbumin following dibutyryl-cyclic AMP-induced differentiation and were killed by IgG from ALS patients. Undifferentiated calbindin/parvalbumin-reactive VSC 4.1 cells were not killed, nor were other cell lines expressing high levels of calbindin-D-28K and parvalbumin immunoreactivity (substantia nigra-neuroblastoma hybrid cells and N18TG2 neuroblastoma parent cells). These studies suggest that decreased calbindin-D-28K and parvalbumin immunoreactivity may help explain the selective vulnerability of motoneurons in ALS.