Proteomic and Targeted Metabolomic Studies on a Silkworm Model of Parkinson's Disease

Parkinson's disease (PD) is a chronic and progressive movement disorder that is characterized by the loss of dopaminergic neurons in the brain. Animal models of PD have become very popular in the past two decades to understand the etiology, pathology, and molecular and cellular pathways associated with PD. In this study, we report the first neurotoxin-induced silkworm model for PD by chronic feeding with 6-hydroxydopamine (6-OHDA) and explore the possible molecular mechanisms associated with PD using proteomic and targeted metabolomic approaches. Although silkworm is phylogenetically distant from humans and rats, 6-OHDA treatment produced similar PD phenotypes, including motor dysfunction, dopaminergic neuron degeneration, and decreased levels of dopamine. Major neurotransmitters in the silkworm head tissue were profiled, revealing key molecules implicating neurodegenerative disorder. Proteomics analysis revealed a major downregulation of nearly 50 structural proteins constituting cuticles and microfilaments, indicating mechanical damage in the silkworm tissues. The results suggest that 6-OHDA treatment could induce PD-like symptoms in silkworms and activate similar proteomic and metabolic pathways to those in rats or higher animals. This study demonstrates the feasibility and value of the silkworm-based PD model, which may provide important clues for understanding the molecular and cellular mechanisms underlying PD. The mass spectrometry raw files have been deposited to iProx via the project ID IPX0004206000.