| First Author | Sargent D | Year | 2018 |
| Journal | Sci Rep | Volume | 8 |
| Issue | 1 | Pages | 17563 |
| PubMed ID | 30510219 | Mgi Jnum | J:269119 |
| Mgi Id | MGI:6271747 | Doi | 10.1038/s41598-018-35825-2 |
| Citation | Sargent D, et al. (2018) Investigating the neuroprotective effect of AAV-mediated beta-synuclein overexpression in a transgenic model of synucleinopathy. Sci Rep 8(1):17563 |
| abstractText | Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases characterized by inclusions mainly composed of alpha-synuclein (alpha-syn) aggregates. The objective of this study was to investigate if beta-synuclein (beta-syn) overexpression could have beneficial effects by inhibiting the aggregation of alpha-syn. The M83 transgenic mouse is a model of synucleinopathy, which develops severe motor symptoms associated with aggregation of alpha-syn. M83 neonate or adult mice were injected with adeno-associated virus vectors carrying the human beta-syn gene (AAVbeta-syn) or green fluorescent protein gene (AAVGFP) using different injection sites. The M83 disease was - or not - accelerated using extracts of M83 brains injected with brain extract from mouse (M83) or human (MSA) origins. AAV vectors expression was confirmed using Western blot and ELISA technics. AAV mediated beta-syn overexpression did not delay the disease onset or reduce the alpha-syn phosphorylated at serine 129 levels detected by ELISA, regardless of the AAV injection route and the inoculation of brain extracts. Instead, a proteinase-K resistant beta-syn staining was detected by immunohistochemistry, specifically in sick M83 mice overexpressing beta-syn after inoculation of AAVbeta-syn. This study indicated for the first time that viral vector-mediated beta-syn overexpression could form aggregates in a model of synucleinopathy. |
