| First Author | El-Agnaf O | Year | 2017 |
| Journal | Neurobiol Dis | Volume | 104 |
| Pages | 85-96 | PubMed ID | 28476636 |
| Mgi Jnum | J:259513 | Mgi Id | MGI:6142847 |
| Doi | 10.1016/j.nbd.2017.05.002 | Citation | El-Agnaf O, et al. (2017) Differential effects of immunotherapy with antibodies targeting alpha-synuclein oligomers and fibrils in a transgenic model of synucleinopathy. Neurobiol Dis 104:85-96 |
| abstractText | Disorders with progressive accumulation of alpha-synuclein (alpha-syn) are a common cause of dementia and parkinsonism in the aging population. Accumulation and propagation of alpha-syn play a role in the pathogenesis of these disorders. Previous studies have shown that immunization with antibodies that recognize C-terminus of alpha-syn reduces the intra-neuronal accumulation of alpha-syn and related deficits in transgenic models of synucleinopathy. These studies employed antibodies that recognize epitopes within monomeric and aggregated alpha-syn that were generated through active immunization or administered via passive immunization. However, it is possible that more specific effects might be achieved with antibodies recognizing selective species of the alpha-syn aggregates. In this respect we recently developed antibodies that differentially recognized various oligomers (Syn-O1, -O2, and -O4) and fibrilar (Syn-F1 and -F2) forms of alpha-syn. For this purpose wild-type alpha-syn transgenic (line 61) mice were immunized with these 5 different antibodies and neuropathologically and biochemically analyzed to determine which was most effective at reducing alpha-syn accumulation and related deficits. We found that Syn-O1, -O4 and -F1 antibodies were most effective at reducing accumulation of alpha-syn oligomers in multiple brain regions and at preventing neurodegeneration. Together this study supports the notion that selective antibodies against alpha-syn might be suitable for development new treatments for synucleinopathies such as PD and DLB. |
