| First Author | Morgan SA | Year | 2020 |
| Journal | J Biol Chem | Volume | 295 |
| Issue | 19 | Pages | 6652-6664 |
| PubMed ID | 32209651 | Mgi Jnum | J:300629 |
| Mgi Id | MGI:6441841 | Doi | 10.1074/jbc.RA119.012179 |
| Citation | Morgan SA, et al. (2020) alpha-Synuclein filaments from transgenic mouse and human synucleinopathy-containing brains are major seed-competent species. J Biol Chem 295(19):6652-6664 |
| abstractText | Assembled alpha-synuclein in nerve cells and glial cells is the defining pathological feature of neurodegenerative diseases called synucleinopathies. Seeds of alpha-synuclein can induce the assembly of monomeric protein. Here, we used sucrose gradient centrifugation and transiently transfected HEK 293T cells to identify the species of alpha-synuclein from the brains of homozygous, symptomatic mice transgenic for human mutant A53T alpha-synuclein (line M83) that seed aggregation. The most potent fractions contained Sarkosyl-insoluble assemblies enriched in filaments. We also analyzed six cases of idiopathic Parkinson's disease (PD), one case of familial PD, and six cases of multiple system atrophy (MSA) for their ability to induce alpha-synuclein aggregation. The MSA samples were more potent than those of idiopathic PD in seeding aggregation. We found that following sucrose gradient centrifugation, the most seed-competent fractions from PD and MSA brains are those that contain Sarkosyl-insoluble alpha-synuclein. The fractions differed between PD and MSA, consistent with the presence of distinct conformers of assembled alpha-synuclein in these different samples. We conclude that alpha-synuclein filaments are the main driving force for amplification and propagation of pathology in synucleinopathies. |
