Journal
SCIENTIFIC REPORTS
Volume 10, Issue 1, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41598-020-62309-z
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Funding
- Brain Research Program through the National Research Foundation of Korea (NRF) - Ministry of Science, ICT & Future Planning [NRF-2017M3C7A1044818]
- National Research Foundation of Korea [2017M3C7A1044818] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
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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.
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