| First Author | Takeda K | Year | 2021 |
| Journal | Commun Biol | Volume | 4 |
| Issue | 1 | Pages | 192 |
| PubMed ID | 33580194 | Mgi Jnum | J:309006 |
| Mgi Id | MGI:6714989 | Doi | 10.1038/s42003-021-01720-2 |
| Citation | Takeda K, et al. (2021) Mitochondrial ubiquitin ligase alleviates Alzheimer's disease pathology via blocking the toxic amyloid-beta oligomer generation. Commun Biol 4(1):192 |
| abstractText | Mitochondrial pathophysiology is implicated in the development of Alzheimer's disease (AD). An integrative database of gene dysregulation suggests that the mitochondrial ubiquitin ligase MITOL/MARCH5, a fine-tuner of mitochondrial dynamics and functions, is downregulated in patients with AD. Here, we report that the perturbation of mitochondrial dynamics by MITOL deletion triggers mitochondrial impairments and exacerbates cognitive decline in a mouse model with AD-related Abeta pathology. Notably, MITOL deletion in the brain enhanced the seeding effect of Abeta fibrils, but not the spontaneous formation of Abeta fibrils and plaques, leading to excessive secondary generation of toxic and dispersible Abeta oligomers. Consistent with this, MITOL-deficient mice with Abeta etiology exhibited worsening cognitive decline depending on Abeta oligomers rather than Abeta plaques themselves. Our findings suggest that alteration in mitochondrial morphology might be a key factor in AD due to directing the production of Abeta form, oligomers or plaques, responsible for disease development. |
