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Interplay between mitophagy and pathogens in neuroinflammation

Research Project

Project/Area Number 23K14675
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 51010:Basic brain sciences-related
Research InstitutionJuntendo University

Principal Investigator

COSSU DAVIDE  順天堂大学, 健康総合科学先端研究機構, 准教授 (90867326)

Project Period (FY) 2023-04-01 – 2026-03-31
Project Status Granted (Fiscal Year 2023)
Budget Amount *help
¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2025: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2024: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2023: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywordsmitochondria / neuroinflammation / Epstein barr virus / endogenous retrovirus / mycobacteria / multiple sclerosis / parkinson'disease / immunity / mitophagy / infection / EAE
Outline of Research at the Start

To investigate the relationships between mitophagy, infections and neuroinflammation, the project is divided into different phases: 1) microbial identification in patients, 2) gene expression analysis in patients, 3) development of animal models to study the effect of mitophagy and infections.

Outline of Annual Research Achievements

We discovered a significant correlation between antibodies targeting Epstein Barr virus (EBV) and human endogenous retrovirus (HERV-W) peptides among a specific subset of Multiple Sclerosis (MS) patients. These findings underscore EBV's involvement in MS pathogenesis, indicating its potential to trigger HERV-W reactivation. Furthermore, our research presents compelling evidence linking Mycobacterium paratuberculosis to the onset or worsening of MS, particularly in a subgroup of patients exhibiting elevated serum IgG4 levels. Additionally, we devised an alternative approach to induce Experimental Autoimmune Encephalomyelitis using heat-killed mycobacterium. Lastly, we uncovered a crucial role played by the immune system and mitochondrial dysfunction in Parkinson's disease.

Current Status of Research Progress
Current Status of Research Progress

1: Research has progressed more than it was originally planned.

Reason

We're uncovering novel antigens from various pathogens that may play a role in neuroinflammation. Antibodies targeting these pathogens could serve as valuable markers for tracking disease progression in multiple sclerosis and other inflammatory disorders. Furthermore, these antigens seem to induce encephalitogenic effects in vivo, particularly in mice lacking mitophagy-related genes.

Strategy for Future Research Activity

To delve into the role of specific immunogenic antigens observed in patients with MS, NMOSD, and MOGAD, we propose immunizing knockout mice exhibiting mitochondrial abnormalities. This will be accomplished through two primary methods: inducing active experimental autoimmune encephalomyelitis (EAE) or utilizing the cuprizone model.

Report

(1 results)
  • 2023 Research-status Report
  • Research Products

    (9 results)

All 2023

All Journal Article (6 results) Presentation (3 results) (of which Int'l Joint Research: 2 results,  Invited: 1 results)

  • [Journal Article] Adjuvant Activity of <em>Mycobacterium paratuberculosis</em> in Enhancing the Immunogenicity of Autoantigens During Experimental Autoimmune Encephalomyelitis2023

    • Author(s)
      Cossu Davide、Tomizawa Yuji、Momotani Eiichi、Yokoyama Kazumasa、Hattori Nobutaka
    • Journal Title

      Journal of Visualized Experiments

      Volume: 195 Issue: 195 Pages: 1-5

    • DOI

      10.3791/65422

    • Related Report
      2023 Research-status Report
  • [Journal Article] Mycobacterium avium subsp. paratuberculosis Antigens Elicit a Strong IgG4 Response in Patients with Multiple Sclerosis and Exacerbate Experimental Autoimmune Encephalomyelitis2023

    • Author(s)
      Cossu Davide、Tomizawa Yuji、Yokoyama Kazumasa、Sakanishi Tamami、Momotani Eiichi、Sechi Leonardo A.、Hattori Nobutaka
    • Journal Title

      Life

      Volume: 13 Issue: 7 Pages: 1437-1437

    • DOI

      10.3390/life13071437

    • Related Report
      2023 Research-status Report
  • [Journal Article] Influence of aging, mitochondrial dysfunction, and inflammation on Parkinson’s disease2023

    • Author(s)
      Cossu Davide、Hattori Nobutaka
    • Journal Title

      Neural Regeneration Research

      Volume: 19 Issue: 6 Pages: 1197-1198

    • DOI

      10.4103/1673-5374.385873

    • Related Report
      2023 Research-status Report
  • [Journal Article] Correlation between antibodies against the pathogenic <scp>pHERV‐W</scp> envelope protein and the inflammatory phase of multiple sclerosis2023

    • Author(s)
      Ruberto Stefano、Cossu Davide、Sechi Leonardo A.
    • Journal Title

      Immunology

      Volume: 171 Issue: 2 Pages: 270-276

    • DOI

      10.1111/imm.13712

    • Related Report
      2023 Research-status Report
  • [Journal Article] The Role of Immune Dysfunction in Parkinson’s Disease Development2023

    • Author(s)
      Cossu Davide、Hatano Taku、Hattori Nobutaka
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 23 Pages: 16766-16766

    • DOI

      10.3390/ijms242316766

    • Related Report
      2023 Research-status Report
  • [Journal Article] Epstein?Barr Virus and Human Endogenous Retrovirus in Japanese Patients with Autoimmune Demyelinating Disorders2023

    • Author(s)
      Cossu Davide、Tomizawa Yuji、Sechi Leonardo Antonio、Hattori Nobutaka
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Issue: 24 Pages: 17151-17151

    • DOI

      10.3390/ijms242417151

    • Related Report
      2023 Research-status Report
  • [Presentation] Role of Epstein-Barr virus and Mycobacterium avium pa ratuberculosis in CNS demyelinating disorders2023

    • Author(s)
      Cossu Davide
    • Organizer
      54th Annual Meeting of the Japanese Society of Neurology
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research
  • [Presentation] Impact of mitophagy and aging on experimental autoimmune encephalomyelitis2023

    • Author(s)
      Cossu Davide
    • Organizer
      Sendai Conference 2023
    • Related Report
      2023 Research-status Report
    • Invited
  • [Presentation] Role of Epstein-Barr virus and Mycobacterium avium ss. paratuberculosis in CNS demyelinating disorders.2023

    • Author(s)
      Cossu Davide
    • Organizer
      53 Italian Society of Microbiology (SIM), Cagliari, Italy
    • Related Report
      2023 Research-status Report
    • Int'l Joint Research

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Published: 2023-04-13   Modified: 2024-12-25  

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