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

Hiroya Kobayashi, Koji Ueda, Satoru Morimoto, Mitsuru Ishikawa, Nicolas Leventoux, Ryogen Sasaki, Yoshifumi Hirokawa, Yasumasa Kokubo, Hideyuki Okano

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)4511-4516
Number of pages6
JournalNeurological Sciences
Volume44
Issue number12
DOIs
Publication statusPublished - 12-2023
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Dermatology
  • Clinical Neurology
  • Psychiatry and Mental health

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