The red chunk title compound [Cu4(S5)2(4-Mepy) 4]?4-Mepy) was obtained by the reaction of copper powder with sulfur powder, potassium sulfide and excess 4-methylpyridine at ambient temperature and normal atmosphere. I...The red chunk title compound [Cu4(S5)2(4-Mepy) 4]?4-Mepy) was obtained by the reaction of copper powder with sulfur powder, potassium sulfide and excess 4-methylpyridine at ambient temperature and normal atmosphere. Its structure was determined by single-crystal X-ray diffraction analysis, and the crystal data for the compound: triclinic, P , a = 9.7442(2), b = 14.124(3), c = 15.410 (3) ? ?= 98.96(3), ?= 93.82(3), ?= 94.08(3)? V = 2083.7(7) ?3, Z = 2, Dc = 1.66 g/cm3, (MoK? = 1.31mm-1, F(000) = 1052,C30H35N5S10Cu4,Mr = 1040.45. The structure was refined to R = 0.0393 and wR = 0.1158 for 9281 independent reflections. The title crystal consists of a neutral complex molecule [Cu4(S5)2(4-CH3C5H4N)4] and a 4-methylpyridine solvent molecule. In the neutral complex, the four Cu atoms are in a distorted tetrahedral arrangement and the nonbonding Cu…Cu distances in the copper tetrahedron range from 3.1414 to 3.8488 , and the CuS bond lengths vary from 2.2839 to 2.3670 ?展开更多
Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidati...Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.展开更多
基金Supported by the Natural Science Foundation of Fujian Education Committee(JB01045)
文摘The red chunk title compound [Cu4(S5)2(4-Mepy) 4]?4-Mepy) was obtained by the reaction of copper powder with sulfur powder, potassium sulfide and excess 4-methylpyridine at ambient temperature and normal atmosphere. Its structure was determined by single-crystal X-ray diffraction analysis, and the crystal data for the compound: triclinic, P , a = 9.7442(2), b = 14.124(3), c = 15.410 (3) ? ?= 98.96(3), ?= 93.82(3), ?= 94.08(3)? V = 2083.7(7) ?3, Z = 2, Dc = 1.66 g/cm3, (MoK? = 1.31mm-1, F(000) = 1052,C30H35N5S10Cu4,Mr = 1040.45. The structure was refined to R = 0.0393 and wR = 0.1158 for 9281 independent reflections. The title crystal consists of a neutral complex molecule [Cu4(S5)2(4-CH3C5H4N)4] and a 4-methylpyridine solvent molecule. In the neutral complex, the four Cu atoms are in a distorted tetrahedral arrangement and the nonbonding Cu…Cu distances in the copper tetrahedron range from 3.1414 to 3.8488 , and the CuS bond lengths vary from 2.2839 to 2.3670 ?
基金supported by the National Natural Science Foundation of China,Nos.82271444(to JP),82271268(to BZ),and 82001346(to YL)the National Key Research and Development Program of China,No.2022YFE0210100(to BZ)。
文摘Parkinson's disease is primarily caused by the loss of dopaminergic neurons in the substantia nigra compacta.Ferroptosis,a novel form of regulated cell death characterized by iron accumulation and lipid peroxidation,plays a vital role in the death of dopaminergic neurons.However,the molecular mechanisms underlying ferroptosis in dopaminergic neurons have not yet been completely elucidated.NADPH oxidase 4 is related to oxidative stress,however,whether it regulates dopaminergic neuronal ferroptosis remains unknown.The aim of this study was to determine whether NADPH oxidase 4 is involved in dopaminergic neuronal ferroptosis,and if so,by what mechanism.We found that the transcriptional regulator activating transcription factor 3 increased NADPH oxidase 4 expression in dopaminergic neurons and astrocytes in an 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced Parkinson's disease model.NADPH oxidase 4 inhibition improved the behavioral impairments observed in the Parkinson's disease model animals and reduced the death of dopaminergic neurons.Moreover,NADPH oxidase 4 inhibition reduced lipid peroxidation and iron accumulation in the substantia nigra of the Parkinson's disease model animals.Mechanistically,we found that NADPH oxidase 4 interacted with activated protein kinase Cαto prevent ferroptosis of dopaminergic neurons.Furthermore,by lowering the astrocytic lipocalin-2 expression,NADPH oxidase 4 inhibition reduced 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine-induced neuroinflammation.These findings demonstrate that NADPH oxidase 4 promotes ferroptosis of dopaminergic neurons and neuroinflammation,which contribute to dopaminergic neuron death,suggesting that NADPH oxidase 4 is a possible therapeutic target for Parkinson's disease.
