Potential Therapeutic Effects of Policosanol from Insect Wax on Caenorhabditis elegans Models of Parkinson’s Disease

• DOI: 10.1007/s11481-022-10057-4
• Publication Date: 2023-01-13T06:07:29Z
• Authors: Chenjing Ma; Ying Feng; Xian Li; Long Sun; Zhao He; Jin Gan; Minjie He; Xin Zhang; Xiaoming Chen
• Keywords: 0301 basic medicine; Dopaminergic Neurons; Parkinson Disease; Neurodegenerative Diseases; 3. Good health; Animals, Genetically Modified; Disease Models, Animal; 03 medical and health sciences; alpha-Synuclein; Animals; Fatty Alcohols; Caenorhabditis elegans; Reactive Oxygen Species; Oxidopamine

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.