Robert Wood Johnson Medical School Institute for Neurological Therapeutics and Department of Neurology, Rutgers Biomedical and Health Sciences, Piscataway, NJ, United States of America.
Burnett School of Biomedical Sciences, UCF College of Medicine, University of Central Florida, Orlando, FL, United States of America.
PLoS One. 2022 Jul 28;17(7):e0272085. doi: 10.1371/journal.pone.0272085. eCollection 2022.
Parkinson's disease (PD) is a neurodegenerative disease characterized by inclusions of aggregated α-synuclein (α-Syn). Oxidative stress plays a critical role in nigrostriatal degeneration and is responsible for α-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 α-synucleinopathy. To model α-Syn induced PD, we stereotactically injected AAV particles overexpressing human α-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-α-Syn overexpression in the SN. Also, NXP031 blocked the propagation of aggregated α-Syn into the hippocampus by alleviating oxidative stress. These results indicate that NXP031 can be a potential therapeutic for PD.
帕金森病（PD）是一种神经退行性疾病，其特征是聚集的α-突触核蛋白（α-Syn）包涵体。氧化应激在黑质纹状体变性中起关键作用，是 PD 中α-Syn 聚集的原因。维生素 C 或抗坏血酸作为一种有效的抗氧化剂，可预防自由基损伤。然而，维生素 C 很容易被氧化，往往会失去其生理活性，限制了其治疗潜力。本研究旨在评估我们开发的新化合物 NXP031（由 Aptamin C 和维生素 C 组成）是否对α-突触核蛋白病具有神经保护作用。为了模拟α-Syn 诱导的 PD，我们通过立体定向注射过表达人α-Syn 的 AAV 颗粒到小鼠的黑质（SN）中。AAV 注射后一周，通过口服灌胃每天给予 NXP031 治疗八周。我们发现，NXP031 的口服给药可通过旋转棒试验改善运动功能障碍，并防止 WT-α-Syn 在 SN 中的过表达引起的黑质多巴胺能神经元的丢失。此外，NXP031 通过减轻氧化应激阻断了聚集的α-Syn 向海马的传播。这些结果表明，NXP031 可能是 PD 的一种潜在治疗方法。
