Administration of AAV-Alpha Synuclein NAC Antibody Improves Locomotor Behavior in Rats Overexpressing Alpha Synuclein

Accumulation of alpha-Synuclein (alpha Syn) in nigral dopaminergic neurons is commonly seen in patients with Parkinson ' s disease (PD). We recently reported that transduction of intracellular single-chain intrabody targeting the 53-87 amino acid residues of human alpha Syn by recombinant adeno associated viral vector (AAV-NAC32) downregulated alpha Syn protein in SH-SY5Y cells and rat brain. This study characterizes the behavioral phenotype and dopaminergic protection in animals receiving AAV-NAC32. Our results show that adult DAT-Cre rats selectively overexpress alpha Syn in nigra dopaminergic neurons after local administration of AAV-DIO-alpha Syn. These animals develop PD-like phenotype, including bradykinesia and loss of tyrosine hydroxylase (TH) immunoreactivity in substantia nigra pars compacta dorsal tier (SNcd). An injection of AAV-NAC32 to nigra produces a selective antibody against alpha Syn and normalizes the behavior. AAV-NAC32 significantly increases TH, while reduces alpha Syn immunoreactivity in SNcd. Altogether, our data suggest that an AAV-mediated gene transfer of NAC32 antibody effectively antagonizes alpha Syn-mediated dopaminergic degeneration in nigra, which may be a promising therapeutic candidate for synucleinopathy or PD.

Automated summary

The study demonstrates that intervention with AAV-NAC32 on alpha-Synuclein in animals can improve PD-like symptoms, including reducing bradykinesia and restoring tyrosine hydroxylase loss. This research provides hope for this intervention technique as a potential therapeutic candidate for PD.