Parkinson’s disease (PD) is a common neurodegenerative disease with unclear pathogenesis. Currently, there are no disease-modifying neuron-protecting drugs to slow down the neuronal degeneration. Mutations in the leu...Parkinson’s disease (PD) is a common neurodegenerative disease with unclear pathogenesis. Currently, there are no disease-modifying neuron-protecting drugs to slow down the neuronal degeneration. Mutations in the leucine-rich repeat kinase 2 (LRRK2) cause genetic forms of PD and contribute to sporadic PD as well. Disruption of LRRK2 kinase functions has become one of the potential mechanisms underlying disease-linked mutation-induced neuronal degeneration. To further characterize the pharmacological effects of a reported LRRK2 kinase inhibitor, LDN-73794, in vitro cell models and a LRRK2 Drosophila PD model were used. LDN-73794 reduced LRRK2 kinase activity in vitro and in vivo. Moreover, LDN-73794 increased survival, improved locomotor activity, and suppressed DA neuron loss in LRRK2 transgenic flies. These results suggest that inhibition of LRRK2 kinase activity can be a potential therapeutic strategy for PD intervention and LDN-73794 could be a potential lead compound for developing neuroprotective therapeutics.展开更多
Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder resulting from a selective loss of dopaminergic neurons. The pathogenesis of PD remains incompletely understood, but increasing evidence f...Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder resulting from a selective loss of dopaminergic neurons. The pathogenesis of PD remains incompletely understood, but increasing evidence from human and animal studies has suggested that oxidative damage contributes to the neuronal loss in PD. In this study, we used rotenone (a mitochondrial complex I inhibitor) based cell and Drosophila models that resemble some key pathological features of PD to test whether curcumin, a potent antioxidant compound, derived from the curry spice turmeric, could protect against rotenone-induced neuronal toxicity. We found that curcumin reduced rotenone induced cell death in SH-SY5Y human neuroblastoma cells and alleviated PD-like symptoms in drosophila via reducing the intracellular and mitochondrial reactive oxygen species (ROS) levels and inhibiting the caspase-3/caspase-9 activity. These results suggest that curcumin is a promising therapeutic compound for PD.展开更多
The tunable propagation properties of 3D Dirac semimetal(DSM)-supported dielectric-loaded surface plasmons structures have been investigated in the THz regime,including the influences of the Fermi level of 3D DSM laye...The tunable propagation properties of 3D Dirac semimetal(DSM)-supported dielectric-loaded surface plasmons structures have been investigated in the THz regime,including the influences of the Fermi level of 3D DSM layer,the fiber shape and operation frequencies.The results indicate that the shape of dielectric fiber affects the hybrid mode significantly,on the condition that if ax(the semi-minor axis length of the dielectric semi-ellipse)is relatively small,the fiber shows good mode confinement and low loss simultaneously,and the figure of merit reaches more than 200.The propagation property can be manipulated in a wide range by changing the Fermi level of 3D DSM,e.g.if the Fermi level varies in the range of 0.05 eV–0.15 eV,the propagation length changes in the range of 9.073×10^(3)–2.715×10^(4)μm,and the corresponding modulation depth is 66.5%.These results are very helpful to understand the tunable mechanisms of the 3D DSM plasmonic devices,such as switchers,modulators,and sensors.展开更多
文摘Parkinson’s disease (PD) is a common neurodegenerative disease with unclear pathogenesis. Currently, there are no disease-modifying neuron-protecting drugs to slow down the neuronal degeneration. Mutations in the leucine-rich repeat kinase 2 (LRRK2) cause genetic forms of PD and contribute to sporadic PD as well. Disruption of LRRK2 kinase functions has become one of the potential mechanisms underlying disease-linked mutation-induced neuronal degeneration. To further characterize the pharmacological effects of a reported LRRK2 kinase inhibitor, LDN-73794, in vitro cell models and a LRRK2 Drosophila PD model were used. LDN-73794 reduced LRRK2 kinase activity in vitro and in vivo. Moreover, LDN-73794 increased survival, improved locomotor activity, and suppressed DA neuron loss in LRRK2 transgenic flies. These results suggest that inhibition of LRRK2 kinase activity can be a potential therapeutic strategy for PD intervention and LDN-73794 could be a potential lead compound for developing neuroprotective therapeutics.
文摘Parkinson’s disease (PD) is a progressive neurodegenerative movement disorder resulting from a selective loss of dopaminergic neurons. The pathogenesis of PD remains incompletely understood, but increasing evidence from human and animal studies has suggested that oxidative damage contributes to the neuronal loss in PD. In this study, we used rotenone (a mitochondrial complex I inhibitor) based cell and Drosophila models that resemble some key pathological features of PD to test whether curcumin, a potent antioxidant compound, derived from the curry spice turmeric, could protect against rotenone-induced neuronal toxicity. We found that curcumin reduced rotenone induced cell death in SH-SY5Y human neuroblastoma cells and alleviated PD-like symptoms in drosophila via reducing the intracellular and mitochondrial reactive oxygen species (ROS) levels and inhibiting the caspase-3/caspase-9 activity. These results suggest that curcumin is a promising therapeutic compound for PD.
基金the Natural Science Foundation of Shanghai under Grant Nos.21ZR1446500Shanghai Local College Capacity Building Project under Grant No.22010503300 and 21010503200+4 种基金the Research Funding of Shanghai Normal University under Grant No.SK202240National Natural Science Foundation of China under Grant Nos.61674106,12073018,U1931205the Funding of Shanghai Municipal Education Commission under Grant No 2019-01-07-00-02-E00032the Funding of Shanghai Municipality Science and Technology Commission under Grant No 19590746000,20070502400,YDZX20203100002498Student Research Project of Shanghai Normal University(undergraduate)under Grant No.22LKY022.
文摘The tunable propagation properties of 3D Dirac semimetal(DSM)-supported dielectric-loaded surface plasmons structures have been investigated in the THz regime,including the influences of the Fermi level of 3D DSM layer,the fiber shape and operation frequencies.The results indicate that the shape of dielectric fiber affects the hybrid mode significantly,on the condition that if ax(the semi-minor axis length of the dielectric semi-ellipse)is relatively small,the fiber shows good mode confinement and low loss simultaneously,and the figure of merit reaches more than 200.The propagation property can be manipulated in a wide range by changing the Fermi level of 3D DSM,e.g.if the Fermi level varies in the range of 0.05 eV–0.15 eV,the propagation length changes in the range of 9.073×10^(3)–2.715×10^(4)μm,and the corresponding modulation depth is 66.5%.These results are very helpful to understand the tunable mechanisms of the 3D DSM plasmonic devices,such as switchers,modulators,and sensors.
