Department of Pharmacology and Toxicology, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.
Mol Neurobiol. 2018 Aug;55(8):6572-6588. doi: 10.1007/s12035-017-0855-1. Epub 2018 Jan 11.
All current treatments of Parkinson's disease (PD) focus on enhancing the dopaminergic effects and providing symptomatic relief; however, they cannot delay the disease progression. Filgrastim, a recombinant methionyl granulocyte colony-stimulating factor, demonstrated neuroprotection in many neurodegenerative and neurological diseases. This study aimed to assess the neuroprotective effects of filgrastim in rotenone-induced rat model of PD and investigate the potential underlying mechanisms of filgrastim actions. The effects of two doses of filgrastim (20 and 40 μg/kg) on spontaneous locomotion, catalepsy, body weight, histology, and striatal dopamine (DA) content, as well as tyrosine hydroxylase (TH) and α-synuclein expression, were evaluated. Then, the effective dose was further tested for its potential anti-inflammatory, neurotrophic, and antiapoptotic effects. Filgrastim (40 μg/kg) prevented rotenone-induced motor deficits, weight reduction, striatal DA depletion, and histological damage. Besides, it significantly inhibited rotenone-induced decrease in TH expression and increase in α-synuclein immunoreactivity in the midbrains and striata of the rats. These effects were associated with reduction of rotenone-induced neuroinflammation, apoptosis, and brain-derived neurotrophic factor depletion. Collectively, these results suggest that filgrastim might be a good candidate for management of PD.
所有目前治疗帕金森病（PD）的方法都集中在增强多巴胺能作用和提供症状缓解上；然而，它们无法延缓疾病进展。非格司亭，一种重组甲硫氨酸粒细胞集落刺激因子，在许多神经退行性和神经疾病中表现出神经保护作用。本研究旨在评估非格司亭在鱼藤酮诱导的 PD 大鼠模型中的神经保护作用，并探讨非格司亭作用的潜在机制。评估了两种剂量的非格司亭（20 和 40μg/kg）对自发运动、僵住、体重、组织学以及纹状体多巴胺（DA）含量、酪氨酸羟化酶（TH）和α-突触核蛋白表达的影响。然后，进一步测试有效剂量是否具有潜在的抗炎、神经营养和抗凋亡作用。非格司亭（40μg/kg）可预防鱼藤酮引起的运动障碍、体重减轻、纹状体 DA 耗竭和组织损伤。此外，它还显著抑制了鱼藤酮诱导的大鼠中脑和纹状体中 TH 表达的降低和 α-突触核蛋白免疫反应性的增加。这些作用与减少鱼藤酮诱导的神经炎症、细胞凋亡和脑源性神经营养因子耗竭有关。总之，这些结果表明非格司亭可能是治疗 PD 的一个良好候选药物。
