2023 Fiscal Year Research-status Report
Interplay between mitophagy and pathogens in neuroinflammation
| Project/Area Number |
23K14675
|
|---|
| Research Institution | Juntendo 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
|
| Keywords | mitochondria / neuroinflammation / Epstein barr virus / endogenous retrovirus / mycobacteria / multiple sclerosis / parkinson'disease / immunity |
|---|
| 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.
|
| Causes of Carryover |
To perform new experiments, publish the results and go to conferences.
|
