NXP031 prevents dopaminergic neuronal loss and oxidative damage in the AAV-WT-alpha-synuclein mouse model of Parkinson's disease

Parkinson's disease (PD) is a neurodegenerative disease characterized by inclusions of aggregated alpha-synuclein (alpha-Syn). Oxidative stress plays a critical role in nigrostriatal degeneration and is responsible for alpha-Syn aggregation in PD. Vitamin C or ascorbic acid acts as an effective antioxidant to prevent free radical damage. However, vitamin C is easily oxidized and often loses its physiological activity, limiting its therapeutic potential. The objective of this study was to evaluate whether NXP031, a new compound we developed consisting of Aptamin C and Vitamin C, is neuroprotective against alpha-synucleinopathy. To model alpha-Syn induced PD, we stereotactically injected AAV particles overexpressing human alpha-Syn into the substantia nigra (SN) of mice. One week after AAV injection, NXP031 was administered via oral gavage every day for eight weeks. We found that oral administration of NXP031 ameliorated motor deficits measured by the rotarod test and prevented the loss of nigral dopaminergic neurons caused by WT-alpha-Syn overexpression in the SN. Also, NXP031 blocked the propagation of aggregated alpha-Syn into the hippocampus by alleviating oxidative stress. These results indicate that NXP031 can be a potential therapeutic for PD.

Automated summary

Parkinson's disease (PD) is a neurodegenerative disease characterized by alpha-synuclein aggregation. Vitamin C and ascorbic acid have been found to prevent the progression of PD. A new compound, NXP031, consisting of Aptamin C and Vitamin C, has shown neuroprotective effects against PD by alleviating oxidative stress.