2021 Fiscal Year Final Research Report
Role of stress-induced transcription factor ATF3 on neurodegeneration of prion diseases
| Project/Area Number |
19H03119
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Review Section |
Basic Section 42020:Veterinary medical science-related
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
|
|---|
| Project Period (FY) |
2019-04-01 – 2022-03-31
|
| Keywords | プリオン / ATF3 / 神経細胞死 / フェロトーシス |
|---|
| Outline of Final Research Achievements |
In this study, we analyzed the role of stress-inducible activating transcription factor 3 (ATF3) in the pathobiology of prion diseases. ATF3-positive cells were significantly increased in the thalamus and pontine nucleus of prion-infected mice, where neuronal cell death is well-observed, and around 80% of ATF-3 positive cells were identified as neurons. Apoptosis were not observed in the thalamus, where pronounced neuronal cell death occurred. The amount of GPx4 in the thalamus tended to decrease with prion infection. The 4-HNE, a marker of lipid peroxidation, was less accumulated in ATF3-positive neurons than ATF3-negative neurons. These results suggested that neurons in the thalamus die of ferroptosis and that induction of ATF3 expression may mitigate lipid peroxidation in the neurons and suppress ferroptosis.
|
| Free Research Field |
獣衛生学、微生物学
|
| Academic Significance and Societal Importance of the Research Achievements |
難治性神経変性疾患の一つであるプリオン病における神経細胞死に、脂質の過酸化が誘因となるフェロトーシスが関与する可能性を世界で初めて見いだしたことは、学術的に大きな意義がある。また、フェロトーシスの抑制が神経細胞死の抑制につながる可能性があり、治療法開発戦略の新たな治療標的となる点でも社会的な意義も大きいと考えられる。
|
