Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older adults.Primary features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neur...Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older adults.Primary features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the cells.While there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are costly and exhibit potential negative side effects.Mounting evidence suggests significant involvement of tau protein in Alzheimer’s disease-related neurodegeneration.As an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal growth.In fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the brain.Various therapeutic strategies targeting tau protein have begun to emerge,and are considered possible methods to prevent and treat Alzheimer’s disease.Specifically,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,contribute to its microtubule dissociation,misfolding,and subcellular missorting.This causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and cognitive deficits.This review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.展开更多
Autism spectrum disorder(ASD)is one of the common neurodevelopmental disorders in children.Its etiology and pathogenesis are poorly understood.Previous studies have suggested potential changes in the complement and co...Autism spectrum disorder(ASD)is one of the common neurodevelopmental disorders in children.Its etiology and pathogenesis are poorly understood.Previous studies have suggested potential changes in the complement and coagulation pathways in individuals with ASD.In this study,using multiple reactions monitoring proteomic technology,16 of the 33 proteins involved in this pathway were identified as differentially-expressed proteins in plasma between children with ASD and controls.Among them,CFHR3,C4BPB,C4BPA,CFH,C9,SERPIND1,C8A,F9,and F11 were found to be altered in the plasma of children with ASD for the first time.SERPIND1 expression was positively correlated with the CARS score.Using the machine learning method,we obtained a panel composed of 12 differentially-expressed proteins with diagnostic potential for ASD.We also reviewed the proteins changed in this pathway in the brain and blood of patients with ASD.The complement and coagulation pathways may be activated in the peripheral blood of children with ASD and play a key role in the pathogenesis of ASD.展开更多
Uncontrolled microglial activation is decisively involved in the neuroinflammatory pathogenesis of brain diseases. Consequently, suppression of microglial overactivation appears to be a strategy for the prevention of ...Uncontrolled microglial activation is decisively involved in the neuroinflammatory pathogenesis of brain diseases. Consequently, suppression of microglial overactivation appears to be a strategy for the prevention of nerve injury. In this paper, a novel vanadium complex, vanadyl N-(p-N,Ndimethylaminophenylcarbamoylmethyl)iminodiacetate(VO(p-dmada)), was synthesized from vanadyl sulfate and N,N-dimethyl-p-phenylenediamine, which was structurally characterized by Fourier transform infrared spectrum and ESI-MS analysis. The effect of VO(p-dmada) on neuroinflammation was investigated by using the models of lipopolysaccharide(LPS)-induced BV2 microglial cells and BALB/c mice.Our data demonstrated that VO(p-dmada) significantly suppressed microglial activation by downregulating inflammatory mediators and associated proteins, and inactivating nuclear factor-κ B(NF-κ B) signaling pathway. VO(p-dmada) also upregulated peroxisome proliferator activated receptor gamma(PPARγ) by reducing transglutaminase 2 and heat shock protein 60 expression. Co-treatment with PPARγ antagonist GW9662 significantly impeded the inhibitory effect of VO(p-dmada) on LPS-induced neuroinflammation.These cumulative findings demonstrated that VO(p-dmada) is a potential new drug for the treatment of neuroinflammation-related neurodegenerative diseases.展开更多
基金supported by the National Natural Science Foundation of China,No.82101493(to JY)。
文摘Alzheimer’s disease is the most prevalent neurodegenerative disease affecting older adults.Primary features of Alzheimer’s disease include extra cellular aggregation of amyloid-βplaques and the accumulation of neurofibrillary tangles,fo rmed by tau protein,in the cells.While there are amyloid-β-ta rgeting therapies for the treatment of Alzheimer’s disease,these therapies are costly and exhibit potential negative side effects.Mounting evidence suggests significant involvement of tau protein in Alzheimer’s disease-related neurodegeneration.As an important microtubule-associated protein,tau plays an important role in maintaining the stability of neuronal microtubules and promoting axonal growth.In fact,clinical studies have shown that abnormal phosphorylation of tau protein occurs before accumulation of amyloid-βin the brain.Various therapeutic strategies targeting tau protein have begun to emerge,and are considered possible methods to prevent and treat Alzheimer’s disease.Specifically,abnormalities in post-translational modifications of the tau protein,including aberrant phosphorylation,ubiquitination,small ubiquitin-like modifier(SUMO)ylation,acetylation,and truncation,contribute to its microtubule dissociation,misfolding,and subcellular missorting.This causes mitochondrial damage,synaptic impairments,gliosis,and neuroinflammation,eventually leading to neurodegeneration and cognitive deficits.This review summarizes the recent findings on the underlying mechanisms of tau protein in the onset and progression of Alzheimer’s disease and discusses tau-targeted treatment of Alzheimer’s disease.
基金supported by the National Natural Science Foundation of China(31870825)the Shenzhen Bureau of Science,Technology,and Information(JCYJ20170412110026229)+1 种基金the Shenzhen-Hong Kong Institute of Brain Science-Shenzhen Fundamental Research Institutions(2022SHIBS0003)2019 Guiyang Science and Technology Bureau,and the Guiyang First People’s Hospital,Great Health Science and Technology Cooperation Project.
文摘Autism spectrum disorder(ASD)is one of the common neurodevelopmental disorders in children.Its etiology and pathogenesis are poorly understood.Previous studies have suggested potential changes in the complement and coagulation pathways in individuals with ASD.In this study,using multiple reactions monitoring proteomic technology,16 of the 33 proteins involved in this pathway were identified as differentially-expressed proteins in plasma between children with ASD and controls.Among them,CFHR3,C4BPB,C4BPA,CFH,C9,SERPIND1,C8A,F9,and F11 were found to be altered in the plasma of children with ASD for the first time.SERPIND1 expression was positively correlated with the CARS score.Using the machine learning method,we obtained a panel composed of 12 differentially-expressed proteins with diagnostic potential for ASD.We also reviewed the proteins changed in this pathway in the brain and blood of patients with ASD.The complement and coagulation pathways may be activated in the peripheral blood of children with ASD and play a key role in the pathogenesis of ASD.
基金financially supported by grants from the National Natural Science Foundation of China(No.21877081)the China Postdoctoral Science Foundation(No.2021M692210)+2 种基金Guangdong Provincial Key S&T Program(No.2018B030336001)the Shenzhen Science and Technology Innovation Commission(No.JCYJ20200109110001818)the Shenzhen-Hong Kong Institute of brain Science-Shenzhen Fundamental Research institutions(No.2022SHIBS0003)。
文摘Uncontrolled microglial activation is decisively involved in the neuroinflammatory pathogenesis of brain diseases. Consequently, suppression of microglial overactivation appears to be a strategy for the prevention of nerve injury. In this paper, a novel vanadium complex, vanadyl N-(p-N,Ndimethylaminophenylcarbamoylmethyl)iminodiacetate(VO(p-dmada)), was synthesized from vanadyl sulfate and N,N-dimethyl-p-phenylenediamine, which was structurally characterized by Fourier transform infrared spectrum and ESI-MS analysis. The effect of VO(p-dmada) on neuroinflammation was investigated by using the models of lipopolysaccharide(LPS)-induced BV2 microglial cells and BALB/c mice.Our data demonstrated that VO(p-dmada) significantly suppressed microglial activation by downregulating inflammatory mediators and associated proteins, and inactivating nuclear factor-κ B(NF-κ B) signaling pathway. VO(p-dmada) also upregulated peroxisome proliferator activated receptor gamma(PPARγ) by reducing transglutaminase 2 and heat shock protein 60 expression. Co-treatment with PPARγ antagonist GW9662 significantly impeded the inhibitory effect of VO(p-dmada) on LPS-induced neuroinflammation.These cumulative findings demonstrated that VO(p-dmada) is a potential new drug for the treatment of neuroinflammation-related neurodegenerative diseases.