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
Multiple sclerosis(MS)is the most common chronic disease of the central nervous system(CNS)in young adults and represents the first cause of severe handicap,originally non-traumatic(Oh et al.,2018).MS is chara cterize...Multiple sclerosis(MS)is the most common chronic disease of the central nervous system(CNS)in young adults and represents the first cause of severe handicap,originally non-traumatic(Oh et al.,2018).MS is chara cterized by the infiltration of auto reactive lymphocytes specific to myelin through the blood-brain barrier,which results in the appearance of inflammatory demyelinating lesions caused by the death of the central nervous system myelinating cells,oligodendrocytes(Oh et al.,2018).There is a prevalence sexual with a ratio of three times more affected women than men.展开更多
It is widely recognized that the development of ZABs is impeded by the kinetic bottleneck of oxygen evolution reaction(OER)and oxygen reduction reaction(ORR).The application of conformational entropy strategy to oxide...It is widely recognized that the development of ZABs is impeded by the kinetic bottleneck of oxygen evolution reaction(OER)and oxygen reduction reaction(ORR).The application of conformational entropy strategy to oxides often involves introducing multiple elements with different properties,thereby providing outstanding bifunctional catalytic activity for OER/ORR.Nevertheless,the possible underlying catalytic pathways and potential interactions between various components are still poorly understood.This paper presents an excellent medium-entropy perovskite oxide,Sr(FeCoNiMo)_(1/4)O_(3−δ)(lower overpotential of 301 mV at 10 mA cm^(−2)).Zinc-air batteries employing it as a cathode catalyst demonstrate excellent round-trip efficiency(62%).By combining theoretical calculation with experiments,we aim to establish the link between the electronic structure of perovskite oxides with different elemental compositions and their OER mechanism.Research reveals that the conformational entropy strategy can simultaneously shift the O 2p-band center and metal d-band center of perovskite oxide towards the vicinity of the Fermi energy level,thereby triggering a more favorable lattice oxygen-participated mechanism(LOM)during the OER process.The outcomes of this work provide crucial insights into the role of conformational entropy strategies in oxygen catalysis and offer potential avenues for constructing efficient and stable electrocatalysts.展开更多
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.
基金supported by a grant from the French Multiple Sclerosis Society(ARSEP,Grant Number:R20163LL)(to AMG)。
文摘Multiple sclerosis(MS)is the most common chronic disease of the central nervous system(CNS)in young adults and represents the first cause of severe handicap,originally non-traumatic(Oh et al.,2018).MS is chara cterized by the infiltration of auto reactive lymphocytes specific to myelin through the blood-brain barrier,which results in the appearance of inflammatory demyelinating lesions caused by the death of the central nervous system myelinating cells,oligodendrocytes(Oh et al.,2018).There is a prevalence sexual with a ratio of three times more affected women than men.
基金the financial support from the National Natural Science Foundation of China (51872067 and 21773048)
文摘It is widely recognized that the development of ZABs is impeded by the kinetic bottleneck of oxygen evolution reaction(OER)and oxygen reduction reaction(ORR).The application of conformational entropy strategy to oxides often involves introducing multiple elements with different properties,thereby providing outstanding bifunctional catalytic activity for OER/ORR.Nevertheless,the possible underlying catalytic pathways and potential interactions between various components are still poorly understood.This paper presents an excellent medium-entropy perovskite oxide,Sr(FeCoNiMo)_(1/4)O_(3−δ)(lower overpotential of 301 mV at 10 mA cm^(−2)).Zinc-air batteries employing it as a cathode catalyst demonstrate excellent round-trip efficiency(62%).By combining theoretical calculation with experiments,we aim to establish the link between the electronic structure of perovskite oxides with different elemental compositions and their OER mechanism.Research reveals that the conformational entropy strategy can simultaneously shift the O 2p-band center and metal d-band center of perovskite oxide towards the vicinity of the Fermi energy level,thereby triggering a more favorable lattice oxygen-participated mechanism(LOM)during the OER process.The outcomes of this work provide crucial insights into the role of conformational entropy strategies in oxygen catalysis and offer potential avenues for constructing efficient and stable electrocatalysts.
