| First Author | Chung HJ | Year | 2020 |
| Journal | Sci Rep | Volume | 10 |
| Issue | 1 | Pages | 5284 |
| PubMed ID | 32210343 | Mgi Jnum | J:292662 |
| Mgi Id | MGI:6445419 | Doi | 10.1038/s41598-020-62309-z |
| Citation | Chung HJ, et al. (2020) The function of bacterial HtrA is evolutionally conserved in mammalian HtrA2/Omi. Sci Rep 10(1):5284 |
| abstractText | Although the malfunction of HtrA2/Omi leads to Parkinson's disease (PD), the underlying mechanism has remained unknown. Here, we showed that HtrA2/Omi specifically removed oligomeric alpha-Syn but not monomeric alpha-Syn to protect oligomeric alpha-Syn-induced neurodegeneration. Experiments using mnd2 mice indicated that HtrA2/Omi degraded oligomeric alpha-Syn specifically without affecting monomers. Transgenic Drosophila melanogaster experiments of the co-expression alpha-Syn and HtrA2/Omi and expression of genes individually also confirmed that pan-neuronal expression of HtrA2/Omi completely rescued Parkinsonism in the alpha-Syn-induced PD Drosophila model by specifically removing oligomeric alpha-Syn. HtrA2/Omi maintained the health and integrity of the brain and extended the life span of transgenic flies. Because HtrA2/Omi specifically degraded oligomeric alpha-Syn, co-expression of HtrA2/Omi and alpha-Syn in Drosophila eye maintained a healthy retina, while the expression of alpha-Syn induced retinal degeneration. This work showed that the bacterial function of HtrA to degrade toxic misfolded proteins is evolutionarily conserved in mammalian brains as HtrA2/Omi. |
