Gonatas N K, Stieber A, Mourelatos Z, Chen Y, Gonatas J O, Appel S H, Hays A P, Hickey W F, Hauw J J
Department of Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104-6079.
Am J Pathol. 1992 Mar;140(3):731-7.
The Golgi apparatus (complex) is at the center stage of important functions of processing and transport of plasma membrane, lysosomal, and secreted proteins. The involvement of the Golgi apparatus in the pathogenesis of chronic degenerative diseases of neurons is virtually unknown. In the present study, fragmentation and atrophy of the Golgi apparatus of motor neurons in amyotrophic lateral sclerosis (ALS), has been detected with organelle specific antibodies. Approximately 30% of motor neurons in five ALS patients showed a fragmented Golgi apparatus whereas only about 1% of motor neurons from seven controls with neurologic or systemic disease showed a similar change. Morphometric studies are consistent with the hypothesis that the alteration of the Golgi apparatus is an early event in the pathogenesis of the neuronal degeneration in ALS. Immunocytochemical studies with antibodies against alpha tubulin, tau, and phosphorylated subunits of neurofilament polypeptides did not disclose differences in the staining of neurons with fragmented or normal Golgi apparatus, suggesting that the alteration of the organelle is not secondary to a gross lesion of the cytoskeleton. However, these observations do not rule out the hypothesis that the fragmentation of the Golgi apparatus is secondary to subtle changes of the polypeptides involved in the attachment of membranes of the organelle to the cytoskeleton.
高尔基体处于质膜、溶酶体及分泌蛋白加工与运输等重要功能的核心位置。高尔基体与神经元慢性退行性疾病发病机制之间的关联实际上尚不清楚。在本研究中，利用细胞器特异性抗体检测到肌萎缩侧索硬化症（ALS）患者运动神经元的高尔基体出现碎片化和萎缩。五名ALS患者中约30%的运动神经元显示高尔基体碎片化，而七名患有神经或全身性疾病的对照者中只有约1%的运动神经元出现类似变化。形态学研究与以下假说相符，即高尔基体的改变是ALS神经元变性发病机制中的早期事件。使用抗α微管蛋白、tau及神经丝多肽磷酸化亚基的抗体进行免疫细胞化学研究，未发现高尔基体碎片化或正常的神经元在染色上存在差异，这表明细胞器的改变并非继发于细胞骨架的严重损伤。然而，这些观察结果并未排除以下假说，即高尔基体的碎片化继发于参与细胞器膜与细胞骨架附着的多肽的细微变化。
