Anti-Human α-Synuclein N-Terminal Peptide Antibody Protects against Dopaminergic Cell Death and Ameliorates Behavioral Deficits in an AAV-α-Synuclein Rat Model of Parkinson’s Disease

摘要: The protein α-synuclein (α-Syn) has a central role in the pathogenesis of Parkinson’s disease (PD) and immunotherapeutic approaches targeting this molecule have shown promising results. In study, novel antibodies were generated against specific peptides from full length human α-Syn evaluated for effectiveness ameliorating α-Syn-induced cell death behavioral deficits an AAV-α-Syn expressing rat model PD. Fisher 344 rats injected with rAAV vector into right substantia nigra (SN), while control received AAV green fluorescent (GFP). Beginning one week after injection vectors, treated intraperitoneally either IgG or N-terminal (AB1), region (AB2) α-Syn. An unbiased stereological estimation TH+, NeuN+, OX6 (MHC-II) immunostaining revealed that peptide (AB1 AB2) significantly inhibited dopaminergic (DA) NeuN+ loss (one-way ANOVA (F (3, 30) = 5.8, p 0.002 29) 7.92, respectively), as well decreasing number activated microglia ipsilateral SN F 14.09; 0.0003). Antibody animals also had lower levels (7, 37) 9.786; 0.0001) demonstrated partial intermediate improvement deficits. Our data suggest that, particular, antibody can protect DA neuron and, to some extent As such, these results may be potential therapeutic strategy halting progression