Amyotrophic lateral sclerosis : on the decreased transcription activity of ribosomal RNA gene and cell degeneration

肌萎缩侧索硬化症：核糖体RNA基因转录活性降低和细胞变性

• 批准号: 14580735
• 负责人: OYANAGI Kiyomitsu
• 金额: $ 2.24万
• 依托单位: Tokyo Metropolitan Organization for Medical Research
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2002
• 资助国家: 日本
• 起止时间: 2002 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14580735/
• 关键词: Amyotrophic lateral sclerosis; ALS; Spinal cord; Anterior horn cell; Ribosome; Rough endoplasmic reticulum; Protein synthesis; Protein infolding; RNA; 転写活性

Morphological changes of the protein synthesizing system including rough ER, molecular chaperon and Golgi apparatus, and transcription activity of ribosomal (r) RNA gene in the anterior horn cells of the patients with amyotrophic lateral sclerosis (ALS) were examined. The present research elucidated that the activity of the transcription of rRNA gene reduced very quickly after insults on the motor neurons, which induced decrease of cytoplasmic rRNA. Localization of molecular chaperon, KDEL, changed earlier than the fragmentation of the Golgi apparatus and decrease of Nissl substance in the anterior horn cells of the patients with ALS. The cisterns of the rER of the anterior horn cells of ALS were dilated irregularly, and the number of the attached ribosomes on the cistern decreased. Thus the protein synthesizing system in the anterior horn cells in ALS patients degenerated from upper stream to downstream.

本文观察了肌萎缩侧索硬化（ALS）患者前角细胞粗面内质网、分子伴侣和高尔基体等蛋白质合成系统的形态学改变，以及核糖体（r）RNA基因转录活性的变化。本研究阐明了运动神经元损伤后rRNA基因转录活性迅速降低，导致胞质rRNA含量减少。ALS患者前角细胞中分子伴侣KDEL的定位变化早于高尔基体断裂和尼氏物质减少。肌萎缩侧索硬化前角细胞rER池不规则扩张，池上附着的核糖体数量减少。因此，ALS患者前角细胞的蛋白质合成系统从上游到下游退化。

项目成果

VAChT-Cre.Fast and VAChT-Cre.Slow: Postnatal expression of Cre recombinase in somatomotor neurons with different onset

• DOI: 10.1002/gene.10224
• 发表时间: 2003-09-01
• 期刊: GENESIS
• 影响因子: 1.5
• 作者: Misawa, H;Nakata, K;Takahashi, R
• 通讯作者: Takahashi, R

Synthesis, localization and externalization of galectin-1 in mature dorsal root ganglion neurons and Schwann cells

成熟背根神经节神经元和雪旺细胞中半乳糖凝集素-1的合成、定位和外化

• 发表时间: 2004
• 期刊: Eur J Neurosci 19
• 作者: Sango K;et al.
• 通讯作者: et al.

Piao Y.-S., et al.: "Neuropathology with clinical correlation of sporadic amyotrophic lateral sclerosis : 102 autopsy cases examined between 1962-2000"Brain Pathology. 12(1). 10-22 (2003)

Piao Y.-S.等人：“散发性肌萎缩侧索硬化症临床相关性的神经病理学：1962-2000年间检查的102例尸检病例”脑病理学。

Amyotrophic lateral sclerosis : on the origin of the degenerated fibers in the white matter of the spinal cord

肌萎缩侧索硬化症：脊髓白质变性纤维的起源

• 发表时间: 2005
• 期刊: Amyotrophic Lateral Sclerosis : New Research (印刷中)
• 作者: Oyanagi K;et al.
• 通讯作者: et al.

Klotho insufficiency causes decrease of ribosomal RNA gene transcription activity, cytoplasmic RNA and rough ER in the spinal anterior horn

Klotho 不足导致脊髓前角核糖体 RNA 基因转录活性、细胞质 RNA 和粗糙 ER 降低

• 期刊: Acta Neuropathol (In press)
• 作者: Anamizu Y;et al.
• 通讯作者: et al.