A D. melanogaster parkin mutant larval model of Parkinson's Disease

摘要: Parkinson’s Disease (PD) is a neurodegenerative disease, with severely reduced movement in patients. The main effect the loss of dopaminergic neurons central nervous system (CNS). Null mutations parkin gene are known to cause PD. I found that Drosophila melanogaster (D. melanogaster) null (dparkin) mutant larvae show neurophysiological abnormalities, bradykinesia-like locomotory defect and synaptic overgrowth at neuromuscular junction (NMJ). Neuronal rescued either muscle or neuronal expression wild-type dparkin larvae. ubiquitous antioxidant enzymes have varying degrees rescue dependent on their properties site action Manipulating c-jun-N-terminal kinase (JNK) signaling components JNK interacting detoxification (Glutathione-s-transferase (GST) Thioredoxin reductase 2 (TRX-R2) ameliorated all types larval phenotypes. Superoxide Dismutase 1 (Sod1) but failed locomotion Additionally, genetically manipulating AMP-activated protein Kinase (AMPK), which involved energy homeostasis, dysfunction not defects. pharmacological manipulation drugs, classical AMPK activators (metformin 5-Aminoimidazole-4-carboxamide ribonucleotide (AICAR)) resveratrol conclude neuronal, rather than muscle, failure key bradykinesia observed suggested be depletion reserve leading dysfunction, oxidative stress. Together these observations suggest stress could downstream consequence metabolic dysfunction.