• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Extensive disruption of connexin gap junction in multiple system atrophy

Research Project

Project/Area Number 21K20873
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund
Review Section 0902:General internal medicine and related fields
Research InstitutionKyushu University

Principal Investigator

Hayashida Shotaro  九州大学, 医学研究院, 共同研究員 (60907385)

Project Period (FY) 2021-08-30 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2022: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2021: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywords多系統萎縮症 / コネキシン / ギャップ結合 / グリア細胞 / シヌクレイン / オリゴデンドロサイト / ミクログリア / マクロファージ
Outline of Research at the Start

多系統萎縮症(multiple system atrophy: MSA)の神経病理学的所見の中核とされるオリゴデンドロサイトにおけるα-synuclein(αSyn)蓄積とグリア細胞質封入体(glial cytoplasmic inclusion: GCI)形成が、どのような経路を介して脱髄や神経細胞死を引き起こすのか未解明な点が多い。私たちは、グリア細胞間情報伝達を担うコネキシン(Cx)蛋白群や、ミクログリア・アストロサイトを含むグリアネットワークに着目し、αSynと脳内恒常性グリアネットワーク破綻という全く新しい視点からMSAの病態解明と新規治療法開発を推進する。

Outline of Final Research Achievements

The pathological hallmark of multiple system atrophy (MSA) is aberrant accumulation of phosphorylated α-synuclein in oligodendrocytes, forming glial cytoplasmic inclusions (GCIs). Extensive demyelination occurs in the olivopontocerebellar and striatonigral pathways. Glial connexins (Cxs) play critical roles in myelin maintenance. We investigated glial Cx changes in 15 autopsied patients with MSA. We classified lesions into three stages: early (Stage I), intermediate (Stage II), and late (Stage III) stages. Accumulation of phosphorylated α-synuclein in oligodendrocytes was frequently seen in Stage I but less frequently observed in Stages II and III. Even at Stage I, Cx32 was absent from myelin. Cx32 was re-distributed in the oligodendrocyte cytoplasm and co-localized with GCIs. Astrocytic Cx43 was down-regulated in Stage I.Early and extensive alterations of glial Cxs occur in MSA and may accelerate demyelination.

Academic Significance and Societal Importance of the Research Achievements

多系統萎縮症は原因不明で進行の速い難治性の神経変性疾患であり、病態解明や新規治療法開発が大きく期待されている。今回の研究成果は多系統萎縮症における脱髄や神経細胞脱落の病態を考える上で、ギャップ結合の破綻という全く新しい機序を提唱したものであり、実際に多系統萎縮症剖検例で検討したことも大きな成果である。今後はギャップ結合やコネキシンに着目した新規治療法開発を推進する。

Report

(3 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • Research Products

    (3 results)

All 2022 2021

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Book (1 results)

  • [Journal Article] Early and extensive alterations of glial connexins, distal oligodendrogliopathy type demyelination, and nodal/paranodal pathology are characteristic of multiple system atrophy2022

    • Author(s)
      Yuji Nishimura, Katsuhisa Masaki, Dai Matsuse, Hiroo Yamaguchi, Tatsunori Tanaka1, Eriko Matsuo, Shotaro Hayashida, Mitsuru Watanabe, Takuya Matsushita, Shoko Sadashima, Naokazu Sasagasako, Ryo Yamasaki, Noriko Isobe, Toru Iwaki, Jun-ichi Kira
    • Journal Title

      Brain Pathology

      Volume: - Issue: 3 Pages: 1-16

    • DOI

      10.1111/bpa.13131

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Paraneoplastic neuromyelitis optica spectrum disorder associated with malignant melanoma: A case report.2021

    • Author(s)
      Morimoto T, Hayashida S, Yamasaki K, Sasahara Y, Takaki T, Yatera K.
    • Journal Title

      Thorac Cancer

      Volume: 12 Issue: 11 Pages: 1775-1779

    • DOI

      10.1111/1759-7714.13965

    • Related Report
      2021 Research-status Report
    • Peer Reviewed
  • [Book] 日本臨床【免疫性神経疾患(第2版)-基礎・臨床の最新知見-】中枢神経脱髄疾患 Tumefactive MS、Balo病2022

    • Author(s)
      林田 翔太郎, 眞崎 勝久
    • Total Pages
      6
    • Publisher
      日本臨床社
    • Related Report
      2022 Annual Research Report

URL: 

Published: 2021-10-22   Modified: 2024-01-30  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi