Ubiquitin Ligase SCarFs Up Internalized α-Synuclein, Prevents Seeding

07 Jun 2019

Can researchers speed the degradation of aggregated, toxic proteins without harming physiological forms? In the June 5 Science Translational Medicine, researchers led by Juan Gerez and Paola Picotti at the Swiss Federal Institute of Technology in Zurich suggest this can work for aggregated α-synuclein, which accumulates in Parkinson’s disease and dementia with Lewy bodies. They identify a specific ubiquitin ligase, SCFFBXL5, that stimulates the degradation of α-synuclein fibrils, but not monomers or oligomers, taken up from the environment by cultured human cells. In wild-type mice, SCFFBXL5 was essential for clearing injected fibrils. Though it remains to be seen if the ligase works the same way in human brain, its components are found in Lewy bodies. The findings suggest that boosting SCFFBXL5activity could help arrest the spread of toxic α-synuclein forms from cell to cell through the brain, the authors propose. It is unclear if the same strategy could also work for other types of aggregated protein.