Fragmentation of the Golgi apparatus in neurodegenerative diseases and cell death
Fragmentation of the Golgi apparatus in neurodegenerative diseases and cell death
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DOI：
10.1016/j.jns.2006.01.019
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发表时间：
2006-07-15
影响因子：
4.4
通讯作者：
Gonatas, Jacqueline O.
中科院分区：
文献类型：
--
作者：
Gonatas, Nicholas K.;Stieber, Anna;Gonatas, Jacqueline O.
据报道，神经元高尔基体 (GA) 碎片在肌萎缩侧索硬化症 (ALS)、皮质基底节变性、阿尔茨海默病和克雅氏病以及 2 型脊髓小脑共济失调 (SCA2) 中出现。在表达家族性ALS（fALS）的铜/锌超氧化物歧化酶（SOD1）G93A突变体的转基因小鼠中，在瘫痪发作前几个月就检测到脊髓运动神经元的GA断裂和突变蛋白聚集。此外，表达 SOD1 的 G93A 和 G85R 突变体的细胞表现出 GA 的碎片化和活力降低，但没有凋亡。我们在此总结了高尔基体碎片化的机制，涉及：(a) 微管不稳定蛋白 Stathmin 的突变体 SOD I 的失调，(b) 神经元细胞质动力蛋白的突变体 SOD1 的破坏，(c) 突变体 SOD1 与Hsp25 和 Hsp27，(d) 聚集的 tau 蛋白减少去酪氨酸化微管，导致非凋亡性细胞死亡，以及 (e) 突变生长激素破坏从粗面内质网到 GA 的运输。数据表明，神经元高尔基体断裂是神经变性中的一种早期且可能不可逆的损伤，由多种机制引起。高尔基体碎裂不是继发于细胞凋亡，但它可能“触发”细胞凋亡。 (c) 2006 Elsevier B.V. 保留所有权利。
Fragmentation of the neuronal Golgi apparatus (GA) was reported in amyotrophic lateral sclerosis (ALS), corticobasal degeneration, Alzheimer's and Creutzfeldt-Jacob disease, and in spinocerebelar ataxia type 2 (SCA2). In transgenic mice expressing the G93A mutant of Cu/Zn superoxide dismutase (SOD1) of familial ALS (fALS), fragmentation of the GA of spinal cord motor neurons and aggregation of mutant protein were detected months before the onset of paralysis. Moreover, cells that expressed the G93A and G85R mutants of SOD1 showed fragmentation of the GA and decreased viability without apoptosis.We summarize here mechanisms involved in Golgi fragmentation implicating: (a) the dysregulation by mutant SOD I of the microtubule-destabilizing protein Stathmin, (b) the disruption by mutant SOD1of the neuronal cytoplasmic dynein, (c) the coprecipitation of mutant SOD1 with Hsp25 and Hsp27, (d) the reduction of detyrosinated microtubules by aggregated tau which resulted in non-apoptotic cell death and (e) the disruption by mutant growth hormone of the trafficking from the rough endoplasmic reticulum to the GA.The data indicate that neuronal Golgi fragmentation is an early and probably irreversible lesion in neurodegeneration, caused by a variety of mechanisms. Golgi fragmentation is not secondary to apoptosis but it may "trigger" apoptosis. (c) 2006 Elsevier B.V. All rights reserved.