Pathological endogenous alpha-synuclein accumulation in oligodendrocyte precursor cells potentially induces inclusions in multiple system atrophy

• Kaji, Seiji

• Maki, Takakuni

• Kinoshita, Hisanori

• Uemura, Norihito

• Ayaki, Takashi

• Kawamoto, Yasuhiro

• Furuta, Takahiro

• URUSHITANI, Makoto

• Hasegawa, Masato

• Kinoshita, Yusuke

• Ono, Yuichi

• Mao, Xiaobo

• Quach, Tran H

• Iwai, Kazuhiro

• Dawson, Valina L

• Dawson, Ted M

• Takahashi, Ryosuke

• 漆谷, 真

Bibliographic Information

Other Title

• Pathological Endogenous α-Synuclein Accumulation in Oligodendrocyte Precursor Cells Potentially Induces Inclusions in Multiple System Atrophy.

Abstract

type:Journal Article

Glial cytoplasmic inclusions (GCIs), commonly observed as α-synuclein (α-syn)-positive aggregates within oligodendrocytes, are the pathological hallmark of multiple system atrophy. The origin of α-syn in GCIs is uncertain; there is little evidence of endogenousα-syn expression in oligodendrocyte lineage cells, oligodendrocyte precursor cells (OPCs),and mature oligodendrocytes (OLGs). Here, based on invitro analysis using primary rat cell cultures, we elucidated that preformed fibrils (PFFs) generated from recombinant human α-syn trigger multimerization and an upsurge of endogenous α-syn in OPCs, which is attributable to insufficient autophagic proteolysis. RNA-seq analysis of OPCs revealed that α-syn PFFs interfered with the expression of proteins associated with neuromodulation and myelination. Furthermore, we detected cytoplasmic α-syn inclusions in OLGs through differentiation of OPCs pre-incubated with PFFs. Overall, our findings suggest the possibility of endogenous α-syn accumulation in OPCs that contributes to GCI formation and perturbation of neuronal/glial support in multiple system atrophy brains.

Journal

• Stem Cell Reports

  Stem Cell Reports 10 (2), 356-365, 2018-01-11

  Cell Press

Keywords

• α-synuclein
• oligodendrocytes
• oligodendrocyte precursor cells
• primary cell culture
• multiple system atrophy
• synucleinopathy
• glial cytoplasmic inclusion
• neurotrophic factor
• misfolding
• autophagy

Details

• CRID: 1050001202934602496
• NII Article ID: 120006377705
• NII Article ID: 120006414715
• ISSN: 22136711
• DOI: 10.1016/j.stemcr.2017.12.001
• HANDLE: 2433/228877
• Web Site: http://hdl.handle.net/10422/00012369
• Web Site: https://api.elsevier.com/content/article/PII:S2213671117305301?httpAccept=text/xml
• Web Site: https://api.elsevier.com/content/article/PII:S2213671117305301?httpAccept=text/plain
• Text Lang: en
• Article Type: journal article
• Data Source:
  • IRDB
  • Crossref
  • CiNii Articles
  • KAKEN