Key Laboratory of Breeding and Utilization of Resource Insects of National Forestry and Grassland Administration, Institute of Highland Forest Science, Chinese Academy of Forestry, Panlong District, Kunming, 650224, Yunnan Province, China.
Health Management Center, The First Affiliated Hospital of Kunming Medical University, Kunming, 650000, Yunnan Province, China.
J Neuroimmune Pharmacol. 2023 Jun;18(1-2):127-144. doi: 10.1007/s11481-022-10057-4. Epub 2023 Jan 13.
Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. The standard treatments for PD focus on symptom relief rather than attempting to address the underlying degenerative processes completely. This study aimed to evaluate the potential therapeutic effects of policosanol derived from insect wax (PIW) by investigating improvements in disease symptoms represented in Caenorhabditis elegans models of PD. For our assessments, we used the following three models: NL5901, which is a transgenic model for α-synuclein aggregation; wild-type N2 induced with 6-hydroxydopamine (6-OHDA); and 6-OHDA-induced BZ555 as a model for loss of dopaminergic neurons (DNs). Specifically, we examined the effects of PIW treatment on α-synuclein aggregation, the loss of DNs, lipid abundance, and the lifespan of treated organisms. Further, we examined treatment-related changes in the levels of reactive oxygen species (ROS), malondialdehyde (MDA), adenosine triphosphate (ATP), glutathione S-transferase (GST), and superoxide dismutase (SOD), as well as the mRNA production profiles of relevant genes. A 10 µg/mL dose of PIW reduced the aggregation of α-synuclein in NL5901 and suppressed the loss of DNs in 6-OHDA-induced BZ555. Overall, PIW treatment decreased ROS and MDA levels, restored lipid abundance, and prolonged the lifespans of worms in all the three models, which may be associated with changes in the expression profiles of genes related to cell survival and oxidative stress response pathways. Our findings show that PIW alleviated the symptoms of PD in these models, possibly by regulating the stress responses initiated by injuries such as α-synuclein aggregation or 6-OHDA treatment.
帕金森病(PD)是全球第二常见的神经退行性疾病。PD 的标准治疗方法侧重于缓解症状,而不是试图完全解决潜在的退行性过程。本研究旨在通过研究 PD 的秀丽隐杆线虫模型中疾病症状的改善来评估来源于昆虫蜡的角鲨烷(PIW)的潜在治疗效果。在我们的评估中,我们使用了以下三种模型:NL5901,这是一种α-突触核蛋白聚集的转基因模型;用 6-羟多巴胺(6-OHDA)诱导的野生型 N2;和 6-OHDA 诱导的 BZ555 作为多巴胺能神经元(DNs)丢失的模型。具体而言,我们研究了 PIW 处理对α-突触核蛋白聚集、DNs 丧失、脂质丰度和处理生物寿命的影响。此外,我们还研究了与治疗相关的活性氧(ROS)、丙二醛(MDA)、三磷酸腺苷(ATP)、谷胱甘肽 S-转移酶(GST)和超氧化物歧化酶(SOD)水平以及相关基因的 mRNA 产生谱的变化。10μg/mL 的 PIW 剂量可减少 NL5901 中α-突触核蛋白的聚集,并抑制 6-OHDA 诱导的 BZ555 中 DNs 的丧失。总体而言,PIW 处理降低了 ROS 和 MDA 水平,恢复了脂质丰度,并延长了所有三种模型中蠕虫的寿命,这可能与与细胞存活和氧化应激反应途径相关的基因表达谱的变化有关。我们的研究结果表明,PIW 减轻了这些模型中 PD 的症状,可能是通过调节由α-突触核蛋白聚集或 6-OHDA 处理等损伤引发的应激反应。