Kobayashi Hiroya, Ueda Koji, Morimoto Satoru, Ishikawa Mitsuru, Leventoux Nicolas, Sasaki Ryogen, Hirokawa Yoshifumi, Kokubo Yasumasa, Okano Hideyuki
Department of Physiology, Keio University School of Medicine, Tokyo, Japan.
Cancer Precision Medicine Center, Japanese Foundation of Cancer Research, Tokyo, Japan.
Neurol Sci. 2023 Dec;44(12):4511-4516. doi: 10.1007/s10072-023-07000-7. Epub 2023 Aug 24.
Amyotrophic lateral sclerosis/Parkinsonism-dementia complex in Kii peninsula, Japan (Kii ALS/PDC), is an endemic neurodegenerative disease whose causes and pathogenesis remain unknown. However, astrocytes in autopsied cases of Kii ALS/PDC show characteristic lesions. In addition, relationships between extracellular vesicles (EVs) and neurodegenerative diseases are increasingly apparent. Therefore, we focused on proteins in EVs derived from Kii ALS/PDC astrocytes in the present study.
Induced pluripotent stem cells (iPSCs) derived from three healthy controls (HCs) and three patients with Kii ALS/PDC were differentiated into astrocytes. EVs in the culture medium of astrocytes were collected and subjected to quantitative proteome analysis.
Our proteome analysis reveals that EV-containing proteins derived from astrocytes of patients with Kii ALS/PDC show distinctive patterns compared with those of HCs. Moreover, EVs derived from Kii ALS/PDC astrocytes display increased proteins related to proteostasis and decreased proteins related to anti-inflammation.
Proteins contained in EVs from astrocytes unveil protective support to neurons and may reflect the molecular pathomechanism of Kii ALS/PDC; accordingly, they may be potential biomarker candidates of Kii ALS/PDC.
日本纪伊半岛的肌萎缩侧索硬化症/帕金森病痴呆综合征（纪伊ALS/PDC）是一种地方性神经退行性疾病，其病因和发病机制尚不清楚。然而，纪伊ALS/PDC尸检病例中的星形胶质细胞显示出特征性病变。此外，细胞外囊泡（EVs）与神经退行性疾病之间的关系日益明显。因此，在本研究中我们聚焦于纪伊ALS/PDC星形胶质细胞衍生的细胞外囊泡中的蛋白质。
将来自三名健康对照（HCs）和三名纪伊ALS/PDC患者的诱导多能干细胞（iPSCs）分化为星形胶质细胞。收集星形胶质细胞培养基中的细胞外囊泡，并进行定量蛋白质组分析。
我们的蛋白质组分析表明，与健康对照相比，纪伊ALS/PDC患者星形胶质细胞衍生的含细胞外囊泡蛋白质呈现出独特的模式。此外，纪伊ALS/PDC星形胶质细胞衍生的细胞外囊泡显示与蛋白质稳态相关的蛋白质增加，而与抗炎相关的蛋白质减少。
星形胶质细胞来源的细胞外囊泡中所含的蛋白质揭示了对神经元的保护支持作用，可能反映了纪伊ALS/PDC的分子病理机制；因此，它们可能是纪伊ALS/PDC潜在的生物标志物候选物。
