corynoxine-b and Parkinson-Disease

Increasing evidence shows that autophagy impairment is involved in the pathogenesis and progression of neurodegenerative diseases including Parkinson's disease (PD). We previously identified a natural alkaloid named corynoxine B (Cory B) as a neuronal autophagy inducer. However, its brain permeability is relatively low, which hinders its potential use in treating PD. Thus we synthesized various derivatives of Cory B to find more potent autophagy inducers with improved brain bioavailability. In this study, we evaluated the autophagy-enhancing effect of CB6 derivative and its neuroprotective action against PD in vitro and in vivo. We showed that CB6 (5-40 μM) dose-dependently accelerated autophagy flux in cultured N2a neural cells through activating the PIK3C3 complex and promoting PI3P production. In MPP

Topics: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; Alkaloids; Animals; Autophagy; Class III Phosphatidylinositol 3-Kinases; Dopaminergic Neurons; Indoles; Mice; Mice, Inbred C57BL; Neuroprotective Agents; Parkinson Disease; Rats; Spiro Compounds