| First Author | Meng L | Year | 2023 |
| Journal | Sci Adv | Volume | 9 |
| Issue | 44 | Pages | eadj1092 |
| PubMed ID | 37910610 | Mgi Jnum | J:342559 |
| Mgi Id | MGI:7546437 | Doi | 10.1126/sciadv.adj1092 |
| Citation | Meng L, et al. (2023) The yeast prion protein Sup35 initiates alpha-synuclein pathology in mouse models of Parkinson's disease. Sci Adv 9(44):eadj1092 |
| abstractText | Parkinson's disease (PD) is characterized by the pathologic aggregation and prion-like propagation of alpha-synuclein (alpha-syn). Emerging evidence shows that fungal infections increase the incidence of PD. However, the molecular mechanisms by which fungi promote the onset of PD are poorly understood. Here, we show that nasal infection with Saccharomyces cerevisiae (S. cerevisiae) in alpha-syn A53T transgenic mice accelerates the aggregation of alpha-syn. Furthermore, we found that Sup35, a prion protein from S. cerevisiae, is the key factor initiating alpha-syn pathology induced by S. cerevisiae. Sup35 interacts with alpha-syn and accelerates its aggregation in vitro. Notably, injection of Sup35 fibrils into the striatum of wild-type mice led to alpha-syn pathology and PD-like motor impairment. The Sup35-seeded alpha-syn fibrils showed enhanced seeding activity and neurotoxicity compared with pure alpha-syn fibrils in vitro and in vivo. Together, these observations indicate that the yeast prion protein Sup35 initiates alpha-syn pathology in PD. |
