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Investigating the neuroprotective effect of AAV-mediated ?-synuclein overexpression in a transgenic model of synucleinopathy.


ABSTRACT: Parkinson's disease (PD) and multiple system atrophy (MSA) are neurodegenerative diseases characterized by inclusions mainly composed of ?-synuclein (?-syn) aggregates. The objective of this study was to investigate if ?-synuclein (?-syn) overexpression could have beneficial effects by inhibiting the aggregation of ?-syn. The M83 transgenic mouse is a model of synucleinopathy, which develops severe motor symptoms associated with aggregation of ?-syn. M83 neonate or adult mice were injected with adeno-associated virus vectors carrying the human ?-syn gene (AAV?-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 ?-syn overexpression did not delay the disease onset or reduce the ?-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 ?-syn staining was detected by immunohistochemistry, specifically in sick M83 mice overexpressing ?-syn after inoculation of AAV?-syn. This study indicated for the first time that viral vector-mediated ?-syn overexpression could form aggregates in a model of synucleinopathy.

PROVIDER: S-EPMC6277436 | BioStudies | 2018-01-01T00:00:00Z

REPOSITORIES: biostudies

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