Background
Parkinson's disease, a prevalent neurodegenerative disease, is characterized by the reduction of dopaminergic neurons resulting in the loss of motor control, resting tremor, the formation of neuronal inclusions and ultimately premature death. Two inherited forms of PD have been linked to mutations in the α-synuclein and parkin genes. The parkin protein functions as an ubiquitin ligase targeting specific proteins for degradation. Expression of human α-synuclein in Drosophila neurons recapitulates the loss of motor control, the development of neuronal inclusions, degeneration of dopaminergic neurons and the ommatidial array to provide an excellent genetic model of PD.Results
To investigate the role of parkin, we have generated transgenic Drosophila that conditionally express parkin under the control of the yeast UAS enhancer. While expression of parkin has little consequence, co-expression of parkin with α-synuclein in the dopaminergic neurons suppresses the α-synuclein-induced premature loss of climbing ability. In addition directed expression of parkin in the eye counteracts the α-synuclein-induced degeneration of the ommatidial array. These results show that parkin suppresses the PD-like symptoms observed in the α-synuclein-dependent Drosophila model of PD.Conclusion
The highly conserved parkin E3 ubiquitin ligase can suppress the damaging effects of human α-synuclein. These results are consistent with a role for parkin in targeting α-synuclein to the proteasome. If this relationship is conserved in humans, this suggests that up-regulation of parkin should suppress α-synucleinopathic PD. The development of therapies that regulate parkin activity may be crucial in the treatment of PD.Pyridine-derived platinum(II) complexes with the general formula [PtCl2L2] (L1: 3,5-dimethylpyridine, L2: 2-amino-5-bromopyridine, L3: 4-(4-nitrobenzyl)pyridine) were synthesized. Characterization of the synthesized complexes was made via FT-IR, UV–Vis, 1H-NMR and 13C-NMR techniques. While the thermal behavior of the complexes was investigated via DTA/TG combined system, their kinetic parameters were investigated by using Flynn–Wall–Ozawa (FWO) and Kissinger–Akahira–Sunose (KAS) methods. The activation energy of the decomposition kinetics of the complexes was calculated to be 196.5–31.7 kJ mol?1 for FWO and 203.4–29.2 kJ mol?1 for KAS. The cytotoxic effect of the complexes against the colon cancer cell line (DLD-1), which is one of the most common types of cancer observed both in humans and animals, was investigated. The complexes showed high cytotoxicity on DLD-1. In particular, [PtCl2L 12 ] complex was found to be the most effective compounds against colon cancer cell line during the 24 h incubation period. According to these results, the pyridine-derived platinum(II) complexes would contribute to oncologic treatment as chemotherapeutic agents.
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