Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 111 Geonjae-ro, Naju-si, Jeollanam-do 58245, Republic of Korea.
Herbal Medicine Resources Research Center, Korea Institute of Oriental Medicine, 111 Geonjae-ro, Naju-si, Jeollanam-do 58245, Republic of Korea.
Neurosci Lett. 2022 Jun 11;781:136667. doi: 10.1016/j.neulet.2022.136667. Epub 2022 Apr 28.
Parkinson disease (PD) is a prevalent neurodegenerative disorder that is characterized by motor and behavioral disturbances, including resting tremors, rigidity, bradykinesia, and postural instability. The primary cause of PD is the degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc) region that subsequently reduces the dopamine content in the striatum (ST); this is a promising therapeutic target for PD. Resilin is an elastomeric protein with high strain, low stiffness, and high resilience that is found in insect cuticles. However, scant evidence supports the application of resilin in neurodegenerative diseases, including PD. Herein, we investigated the protective effects of resilin on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in mouse models and explored the mechanisms underlying its action. Resilin significantly and concentration-dependently reduced 1-methyl-4-phenylpyridinium (MPP)-induced apoptotic neurotoxicity in differentiated PC12 and SH-SY5Y cells. Moreover, resilin prevented dopamine depletion in ST, and immunohistochemical findings indicated that resilin protects against dopaminergic neuronal loss induced by MPTP in the SNpc and ST. Behavioral studies using pole and rotarod tests showed significantly improved PD-related motor impairment in mice treated with resilin. We then explored the molecular mechanisms underlying the apoptosis of dopaminergic neurons using protein arrays and discovered that resilin inhibits dopaminergic neuronal death through the apoptosis signaling factors cytochrome c and caspases-9 and -3 in the SNpc. Thus, resilin has potential in treating PD by controlling apoptosis signals.
帕金森病（PD）是一种常见的神经退行性疾病，其特征为运动和行为障碍，包括静止性震颤、僵直、运动迟缓以及姿势不稳。PD 的主要病因是黑质致密部（SNpc）区多巴胺能神经元退化，进而导致纹状体（ST）中的多巴胺含量降低；这是 PD 的一个有前途的治疗靶点。 弹性蛋白是一种具有高应变、低刚度和高回弹性的弹性蛋白，存在于昆虫的外骨骼中。然而，几乎没有证据支持弹性蛋白在神经退行性疾病，包括 PD 中的应用。在此，我们研究了弹性蛋白对 1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）诱导的 PD 小鼠模型的保护作用，并探讨了其作用机制。弹性蛋白可显著且浓度依赖性地降低分化的 PC12 和 SH-SY5Y 细胞中 1-甲基-4-苯基吡啶鎓（MPP）诱导的凋亡性神经毒性。此外，弹性蛋白可防止 ST 中的多巴胺耗竭，免疫组织化学结果表明弹性蛋白可防止 MPTP 诱导的 SNpc 和 ST 中的多巴胺能神经元丢失。使用杆和转棒试验进行的行为研究表明，用弹性蛋白治疗的小鼠的 PD 相关运动障碍明显改善。然后，我们使用蛋白质阵列探索了多巴胺能神经元凋亡的分子机制，发现弹性蛋白通过 SNpc 中的凋亡信号因子细胞色素 c 和半胱天冬酶-9 和 -3 抑制多巴胺能神经元死亡。因此，弹性蛋白通过控制凋亡信号具有治疗 PD 的潜力。
