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.