| First Author | Koch Y | Year | 2016 |
| Journal | Am J Pathol | Volume | 186 |
| Issue | 8 | Pages | 2152-2161 |
| PubMed ID | 27322773 | Mgi Jnum | J:234276 |
| Mgi Id | MGI:5789666 | Doi | 10.1016/j.ajpath.2016.04.008 |
| Citation | Koch Y, et al. (2016) Aggregated alpha-Synuclein Increases SOD1 Oligomerization in a Mouse Model of Amyotrophic Lateral Sclerosis. Am J Pathol 186(8):2152-61 |
| abstractText | Aggregation of misfolded disease-related proteins is a hallmark of neurodegenerative diseases. Aggregate propagation accompanying disease progression has been demonstrated for different proteins (eg, for alpha-synuclein). Additional evidence supports aggregate cross-seeding activity for alpha-synuclein. For mutated superoxide dismutase 1 (SOD1), which causes familial amyotrophic lateral sclerosis (ALS), self-propagation of aggregation and cell-to-cell transmission have been demonstrated in vitro. However, there is a prominent lack of in vivo data concerning aggregation and cross-aggregation processes of SOD1. We analyzed the effect of alpha-synuclein and SOD1 seeds in cell culture using protein fragment complementation assay and intracerebral injection of alpha-synuclein and SOD1 seeds into SOD1(G93A) transgenic ALS mice. Survival of injected mice was determined, and SOD1 aggregates in the facial nuclei were quantified during disease course. We found that alpha-synuclein preformed fibrils increased the oligomerization rate of SOD1 in vivo and in vitro, whereas aggregated SOD1 did not exert any effect in both experimental setups. Notably, survival of ALS mice was not changed after inoculation of preformed fibrils. We conclude that misfolded alpha-synuclein can increase SOD1 aggregation and suppose that alpha-synuclein seeds are transported from the temporal cortex to the facial nuclei. However, unlike other proteins, the further enhancement of a self-aggregation process by additional SOD1 could not be confirmed in our models. |
