Protein profiling of extracellular vesicles from iPSC-derived astrocytes of patients with ALS/PDC in Kii peninsula

• Published in: Neurological sciences Vol. 44; no. 12; pp. 4511 - 4516
• Main Authors: Kobayashi, Hiroya, Ueda, Koji, Morimoto, Satoru, Ishikawa, Mitsuru, Leventoux, Nicolas, Sasaki, Ryogen, Hirokawa, Yoshifumi, Kokubo, Yasumasa, Okano, Hideyuki
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.12.2023; Springer Nature B.V
• Subjects: Amyotrophic lateral sclerosis; Astrocytes; Basal ganglia; Brief Communication; Cell culture; Central nervous system diseases; Dementia disorders; Extracellular vesicles; Inhibitory postsynaptic potentials; Medicine; Medicine & Public Health; Movement disorders; Neurodegenerative diseases; Neurology; Neuroradiology; Neurosciences; Neurosurgery; Pluripotency; Proteins; Proteomes; Psychiatry; Stem cells; Kii peninsula; Astrocyte; Extracellular vesicle; ALS/PDC; iPSC; Proteome analysis
• ISSN: 1590-1874; 1590-3478
• DOI: 10.1007/s10072-023-07000-7

Background 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. Methods 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. Results 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. Discussion 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.