Current hypothesis of neuronal degeneration in Parkinson＇s disease （PD） have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor defic...Current hypothesis of neuronal degeneration in Parkinson＇s disease （PD） have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor deficiency, inflammatory processes, genetic factors, environmental impact factors, toxic action of nitric oxide, apoptosis, and so on. This review mainly discussed oxidative stress, environmental impact factors, and inflammatory processes in PD.展开更多
Current hypothesis of neuronal degeneration in Parkinson’s disease (PD) have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor deficie...Current hypothesis of neuronal degeneration in Parkinson’s disease (PD) have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor deficiency, inflam- matory processes, genetic factors, environmental impact factors, toxic action of nitric oxide, apoptosis, and so on. This review mainly discussed oxidative stress, environmental impact factors, and inflammatory processes in PD.展开更多
Biomarkers are very important indicators of normal and abnormal biological processes. Specific changes in pathologies, biochemistries and genetics can give us comprehensive information regarding the nature of any part...Biomarkers are very important indicators of normal and abnormal biological processes. Specific changes in pathologies, biochemistries and genetics can give us comprehensive information regarding the nature of any particular disease. A good biomarker should be precise and reliable, distinguishable between normal and interested disease, and differential between different diseases. It is believed that biomarkers have great potential in predicting chances for diseases, aiding in early diagnosis, and setting standards for the development of new remedies to treat diseases. New technologies have enabled scientists to identify biomarkers of several different neurodegenerative diseases. The followings, for instance, are only a few of the many new biomarkers that have been recently identified: the phosphorylated tau protein and aggregated β-amyloid peptide for Alzheimer’s disease (AD), α-synuclein contained Lewy bodies and altered dopamine transporter (DAT) imaging for Parkinson’s disease (PD), SOD mutations for familial amyotrophic lateral sclerosis (ALS), and CAG repeats resulted from Huntington’s gene mutations in Huntington’s disease (HD). This article will focus on the most-recent findings of biomarkers belonging to the four mentioned neurodegenerative diseases.展开更多
Parkinson’s disease (PD) is one of the commonest neurodegenerative disorders characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra and the appearance of Lewy bodies (LBs), whose cytoplas...Parkinson’s disease (PD) is one of the commonest neurodegenerative disorders characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra and the appearance of Lewy bodies (LBs), whose cytoplasmic inclusions are highly enriched with ubiquitin, synphilin-1, α-synuclein and parkin. Synphilin-1 is an α-synuclein-binding protein and a major component of LBs. It is widely accepted that synphilin-1 is involved in the pathogenic process of PD. This review will provide an overall view of the role of synphilin-1 in the pathogenesis of Parkinson’s disease and the latest findings in this field.展开更多
Objective:To explore the relationship between polymorphism of α2-macroglobulin(A2M) gene and Parkinson’s disease(PD)in Han Nationality in Shanghai.Methods:The distributions of A2M gene polymorphism (a Val1000Ile in ...Objective:To explore the relationship between polymorphism of α2-macroglobulin(A2M) gene and Parkinson’s disease(PD)in Han Nationality in Shanghai.Methods:The distributions of A2M gene polymorphism (a Val1000Ile in exon24, V/I)were detected in 66 PD patients and 120 healthy controls using polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP) method. Results:The I allelic frequency in A2M exon24 gene of PD patients(90.9%) was significantly lower than that of the healthy controls(96.3%)(OR=0.39,P=0.033),so was the I/I genotype(OR=0.32,P=0.015), especially in the patients more than 60 years old(OR=0.31,P=0.04).Conclusion:The I allele in exon24 of A2M gene might inhibit the onset of PD in Han Nationality in Shanghai.展开更多
Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes,public health decision making,and primary prevention synthesis.Lead is one of the neuro...Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes,public health decision making,and primary prevention synthesis.Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies.Biomarkers are generally classified into three groups:biomarkers of exposure,effect,and susceptibility.The main body compartments that store lead are the blood,soft tissues,and bone;the half-life of lead in these tissues is measured in weeks for blood,months for soft tissues,and years for bone.Within the brain,lead-induced damage in the prefrontal cerebral cortex,hippocampus,and cerebellum can lead to a variety of neurological disorders,such as brain damage,mental retardation,behavioral problems,nerve damage,and possibly Alzheimer’s disease,Parkinson’s disease,and schizophrenia.This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.展开更多
Microglial activation plays an important role in a panel of neurological disorders such as multiple sclerosis(MS) and Parkinson's disease(PD),and is a key target for developing therapeutic strategies for these dis...Microglial activation plays an important role in a panel of neurological disorders such as multiple sclerosis(MS) and Parkinson's disease(PD),and is a key target for developing therapeutic strategies for these diseases.Ketogenic diet (KD),which is able to inhibit microglial activation in substantia nigra pars compacta of mice,has been shown effective in a mouse model of PD,possibly through increasing D-β-hydroxybutyrate(D-β-HB),a major component of ketone bodies.To verify this,we developed an in vitro model of microglia activation with a microglia line,BV-2,and investigated how D-β-HB have an effect on the LPS-stimulated BV-2 cells.We found D-β-HB is able to recover the cell viability,and inhibit the production of inflammatory mediators and cytokines such as ROS,nitrite,IL-1β,TNF-α,and IL-6,which otherwise were increased in LPS-stimulated BV-2 cells.We conclude that the LPS induced BV-2 cells activation is a valid in vitro model of microglia activation.D-β-HB is able to suppress the activation of BV-2 cells, which might account for one of the possible reasons of KD therapy on the PD model.展开更多
The persistence of beta oscillations generated in the basal ganglia is typical pathological characteristic of Parkin-son's disease.In this paper,we construct a new network model,which is mainly composed of the sub...The persistence of beta oscillations generated in the basal ganglia is typical pathological characteristic of Parkin-son's disease.In this paper,we construct a new network model,which is mainly composed of the subthalamic nu-cleus and the globus pallidus.Based on theory analysis,we obtained the beta shock conditions in the proposed model.It is shown that numerical simulations are in good agreement with analytical results.At last,the effects of cortex and striatum inputs on the generation of oscillations are also discussed.We hope that the obtained results may find applications to treatment of Parkinson’s disease and study of neural oscillations produced in other parts of the brain neural network.展开更多
Objective To observe the effect of acupuncture on the intestinal flora in Parkinson disease(PD)model mice and explore the mechanism of acupuncture in improving the locomotor function in PD.Methods Thirty-two C57BL/6 m...Objective To observe the effect of acupuncture on the intestinal flora in Parkinson disease(PD)model mice and explore the mechanism of acupuncture in improving the locomotor function in PD.Methods Thirty-two C57BL/6 mice were randomly divided into a control group,a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)group,a MPTP+acupuncture group(MPTP+A),and a MPTP+madopar group(MPTP+M),with 8 mice in each group.Except for the control group,the other groups were intraperitoneally injected[25 mg/(kg·bw)]with MPTP to establish PD mouse models.After successful modeling,the MPTP group received no intervention,the MPTP+A received acupuncture at Tianshu(ST25),Guanyuan(CV4),and Zusanli(ST36),and the MPTP+M was given madopar[125 mg/(kg·bw)]by intragastric gavage.After consecutive 10-day interventions,the intestinal function and behaviors of the mice were detected.The 16S rRNA gene sequence was used to analyze the composition of fecal intestinal flora in each group.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and enzyme-linked immunosorbent assay were used to detect the expression levels of inflammatory cytokines in the brain and serum.The expression levels of tyrosine hydroxylase(TH)andα-synuclein in the substantia nigra(SN)were detected by immunohistochemical staining.Toll-like receptor(TLR)2 and lipopolysaccharide receptor CD14(CD14)in the SN were determined by RT-qPCR.Myeloid differentiation factor(MyD)88,nuclear factor kappa-B(NF-κB)and Akt1 in the SN were detected by Western blotting.Results After the intervention,compared with the control group,the intestinal motility,fecal water content,and the expression of TH in the SN were significantly decreased in the MPTP group(P<0.05),along with an increasedα-synuclein expression(P<0.05).Additionally,the results of the fecal microflora test showed that the alpha diversity of the MPTP decreased,and the levels of inflammatory cytokines[tumor necrosis factor(TNF)-α,inducible nitric oxide synthase(iNOS),interleukin(IL)-1β,and IL-6]in the serum and SN,and the expression of NF-κB in the SN were significantly increased(P<0.05).Compared with the MPTP group,acupuncture intervention significantly enhanced the autonomous horizontal movement and coordination ability of PD mice(P<0.05);acupuncture and madopar interventions significantly reduced the levels ofα-synuclein,inflammatory cytokines(TNF-α,iNOS,IL-1β,and IL-6)in the serum and SN,and the NF-κB expression in the SN,along with significantly increased alpha diversity richness index(P<0.05).In addition,the relative abundance of Bacteroides increased significantly in the MPTP+A(P<0.05),while the relative abundance of Firmicutes and Cyanobacteria decreased significantly(P<0.05).Conclusion Acupuncture intervention can improve locomotor function,reduceα-synuclein aggregation and inflammatory factors expression,and increase the Akt signaling pathway in PD mice.In addition,acupuncture intervention can benignly regulate the intestinal flora of PD mice.Therefore,it suggests that acupuncture intervention can protect PD model mice probably by regulating intestinal flora and activating Akt signaling pathway.展开更多
During the past three decades, the Wingless-type MMTV integration site （Wnt） signaling cascade has emerged as an essential system regulating multiple processes in developing and adult brain. Accumulating evidence po...During the past three decades, the Wingless-type MMTV integration site （Wnt） signaling cascade has emerged as an essential system regulating multiple processes in developing and adult brain. Accumulating evidence points to a dysregulation of Wnt signaling in major neurodegenerative pathologies including Parkinson＇s disease （PD）, a common neurodegenerative disorder characterized by the pro- gressive loss of midbrain dopaminergic （mDA） neurons and deregulated activation of astrocytes and microglia. This review highlights the emerging link between Wnt signaling and key inflammatory pathways during mDA neuron damage/repair in PD progression. In particular, we summarize recent evidence documenting that aging and neurotoxicant exposure strongly antagonize Wnt/β-catenin signaling in mDA neurons and subventricular zone （SVZ） neuroprogenitors via astrocyte-microglial interactions. Dysregulation of the crosstalk between Wnt/β-catenin signaling and anti-oxidant/anti-inflammatory pathways delineate novel mechanisms driving the decline of SVZ plasticity with age and the limited nigrostriatal dopaminergic self-repair in PD. These findings hold a promise in devetoping therapies that target Wnt/β-catenin signaling to enhance endogenous restoration and neuronal outcome in age-dependent diseases, such as PD.展开更多
文摘Current hypothesis of neuronal degeneration in Parkinson＇s disease （PD） have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor deficiency, inflammatory processes, genetic factors, environmental impact factors, toxic action of nitric oxide, apoptosis, and so on. This review mainly discussed oxidative stress, environmental impact factors, and inflammatory processes in PD.
文摘Current hypothesis of neuronal degeneration in Parkinson’s disease (PD) have been proposed, including formation of free radicals and oxidative stress, mitochondrial dysfunction, excitotoxicity, trophic factor deficiency, inflam- matory processes, genetic factors, environmental impact factors, toxic action of nitric oxide, apoptosis, and so on. This review mainly discussed oxidative stress, environmental impact factors, and inflammatory processes in PD.
文摘Biomarkers are very important indicators of normal and abnormal biological processes. Specific changes in pathologies, biochemistries and genetics can give us comprehensive information regarding the nature of any particular disease. A good biomarker should be precise and reliable, distinguishable between normal and interested disease, and differential between different diseases. It is believed that biomarkers have great potential in predicting chances for diseases, aiding in early diagnosis, and setting standards for the development of new remedies to treat diseases. New technologies have enabled scientists to identify biomarkers of several different neurodegenerative diseases. The followings, for instance, are only a few of the many new biomarkers that have been recently identified: the phosphorylated tau protein and aggregated β-amyloid peptide for Alzheimer’s disease (AD), α-synuclein contained Lewy bodies and altered dopamine transporter (DAT) imaging for Parkinson’s disease (PD), SOD mutations for familial amyotrophic lateral sclerosis (ALS), and CAG repeats resulted from Huntington’s gene mutations in Huntington’s disease (HD). This article will focus on the most-recent findings of biomarkers belonging to the four mentioned neurodegenerative diseases.
文摘Parkinson’s disease (PD) is one of the commonest neurodegenerative disorders characterized by the loss of dopaminergic (DAergic) neurons in the substantia nigra and the appearance of Lewy bodies (LBs), whose cytoplasmic inclusions are highly enriched with ubiquitin, synphilin-1, α-synuclein and parkin. Synphilin-1 is an α-synuclein-binding protein and a major component of LBs. It is widely accepted that synphilin-1 is involved in the pathogenic process of PD. This review will provide an overall view of the role of synphilin-1 in the pathogenesis of Parkinson’s disease and the latest findings in this field.
文摘Objective:To explore the relationship between polymorphism of α2-macroglobulin(A2M) gene and Parkinson’s disease(PD)in Han Nationality in Shanghai.Methods:The distributions of A2M gene polymorphism (a Val1000Ile in exon24, V/I)were detected in 66 PD patients and 120 healthy controls using polymerase chain reaction and restriction fragment length polymorphism(PCR-RFLP) method. Results:The I allelic frequency in A2M exon24 gene of PD patients(90.9%) was significantly lower than that of the healthy controls(96.3%)(OR=0.39,P=0.033),so was the I/I genotype(OR=0.32,P=0.015), especially in the patients more than 60 years old(OR=0.31,P=0.04).Conclusion:The I allele in exon24 of A2M gene might inhibit the onset of PD in Han Nationality in Shanghai.
文摘Appropriate selection and measurement of lead biomarkers of exposure are critically important for health care management purposes,public health decision making,and primary prevention synthesis.Lead is one of the neurotoxicants that seems to be involved in the etiology of psychologies.Biomarkers are generally classified into three groups:biomarkers of exposure,effect,and susceptibility.The main body compartments that store lead are the blood,soft tissues,and bone;the half-life of lead in these tissues is measured in weeks for blood,months for soft tissues,and years for bone.Within the brain,lead-induced damage in the prefrontal cerebral cortex,hippocampus,and cerebellum can lead to a variety of neurological disorders,such as brain damage,mental retardation,behavioral problems,nerve damage,and possibly Alzheimer’s disease,Parkinson’s disease,and schizophrenia.This paper presents an overview of biomarkers of lead exposure and discusses the neurotoxic effects of lead with regard to children and adults.
文摘Microglial activation plays an important role in a panel of neurological disorders such as multiple sclerosis(MS) and Parkinson's disease(PD),and is a key target for developing therapeutic strategies for these diseases.Ketogenic diet (KD),which is able to inhibit microglial activation in substantia nigra pars compacta of mice,has been shown effective in a mouse model of PD,possibly through increasing D-β-hydroxybutyrate(D-β-HB),a major component of ketone bodies.To verify this,we developed an in vitro model of microglia activation with a microglia line,BV-2,and investigated how D-β-HB have an effect on the LPS-stimulated BV-2 cells.We found D-β-HB is able to recover the cell viability,and inhibit the production of inflammatory mediators and cytokines such as ROS,nitrite,IL-1β,TNF-α,and IL-6,which otherwise were increased in LPS-stimulated BV-2 cells.We conclude that the LPS induced BV-2 cells activation is a valid in vitro model of microglia activation.D-β-HB is able to suppress the activation of BV-2 cells, which might account for one of the possible reasons of KD therapy on the PD model.
基金supported by the National Natural Science Foundation of China(Grant Nos.11325208,11172017)the Research Fund for the Doctoral Program of Higher Education(Grant No.20121102110014)
文摘The persistence of beta oscillations generated in the basal ganglia is typical pathological characteristic of Parkin-son's disease.In this paper,we construct a new network model,which is mainly composed of the subthalamic nu-cleus and the globus pallidus.Based on theory analysis,we obtained the beta shock conditions in the proposed model.It is shown that numerical simulations are in good agreement with analytical results.At last,the effects of cortex and striatum inputs on the generation of oscillations are also discussed.We hope that the obtained results may find applications to treatment of Parkinson’s disease and study of neural oscillations produced in other parts of the brain neural network.
文摘Objective To observe the effect of acupuncture on the intestinal flora in Parkinson disease(PD)model mice and explore the mechanism of acupuncture in improving the locomotor function in PD.Methods Thirty-two C57BL/6 mice were randomly divided into a control group,a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)group,a MPTP+acupuncture group(MPTP+A),and a MPTP+madopar group(MPTP+M),with 8 mice in each group.Except for the control group,the other groups were intraperitoneally injected[25 mg/(kg·bw)]with MPTP to establish PD mouse models.After successful modeling,the MPTP group received no intervention,the MPTP+A received acupuncture at Tianshu(ST25),Guanyuan(CV4),and Zusanli(ST36),and the MPTP+M was given madopar[125 mg/(kg·bw)]by intragastric gavage.After consecutive 10-day interventions,the intestinal function and behaviors of the mice were detected.The 16S rRNA gene sequence was used to analyze the composition of fecal intestinal flora in each group.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)and enzyme-linked immunosorbent assay were used to detect the expression levels of inflammatory cytokines in the brain and serum.The expression levels of tyrosine hydroxylase(TH)andα-synuclein in the substantia nigra(SN)were detected by immunohistochemical staining.Toll-like receptor(TLR)2 and lipopolysaccharide receptor CD14(CD14)in the SN were determined by RT-qPCR.Myeloid differentiation factor(MyD)88,nuclear factor kappa-B(NF-κB)and Akt1 in the SN were detected by Western blotting.Results After the intervention,compared with the control group,the intestinal motility,fecal water content,and the expression of TH in the SN were significantly decreased in the MPTP group(P<0.05),along with an increasedα-synuclein expression(P<0.05).Additionally,the results of the fecal microflora test showed that the alpha diversity of the MPTP decreased,and the levels of inflammatory cytokines[tumor necrosis factor(TNF)-α,inducible nitric oxide synthase(iNOS),interleukin(IL)-1β,and IL-6]in the serum and SN,and the expression of NF-κB in the SN were significantly increased(P<0.05).Compared with the MPTP group,acupuncture intervention significantly enhanced the autonomous horizontal movement and coordination ability of PD mice(P<0.05);acupuncture and madopar interventions significantly reduced the levels ofα-synuclein,inflammatory cytokines(TNF-α,iNOS,IL-1β,and IL-6)in the serum and SN,and the NF-κB expression in the SN,along with significantly increased alpha diversity richness index(P<0.05).In addition,the relative abundance of Bacteroides increased significantly in the MPTP+A(P<0.05),while the relative abundance of Firmicutes and Cyanobacteria decreased significantly(P<0.05).Conclusion Acupuncture intervention can improve locomotor function,reduceα-synuclein aggregation and inflammatory factors expression,and increase the Akt signaling pathway in PD mice.In addition,acupuncture intervention can benignly regulate the intestinal flora of PD mice.Therefore,it suggests that acupuncture intervention can protect PD model mice probably by regulating intestinal flora and activating Akt signaling pathway.
文摘During the past three decades, the Wingless-type MMTV integration site （Wnt） signaling cascade has emerged as an essential system regulating multiple processes in developing and adult brain. Accumulating evidence points to a dysregulation of Wnt signaling in major neurodegenerative pathologies including Parkinson＇s disease （PD）, a common neurodegenerative disorder characterized by the pro- gressive loss of midbrain dopaminergic （mDA） neurons and deregulated activation of astrocytes and microglia. This review highlights the emerging link between Wnt signaling and key inflammatory pathways during mDA neuron damage/repair in PD progression. In particular, we summarize recent evidence documenting that aging and neurotoxicant exposure strongly antagonize Wnt/β-catenin signaling in mDA neurons and subventricular zone （SVZ） neuroprogenitors via astrocyte-microglial interactions. Dysregulation of the crosstalk between Wnt/β-catenin signaling and anti-oxidant/anti-inflammatory pathways delineate novel mechanisms driving the decline of SVZ plasticity with age and the limited nigrostriatal dopaminergic self-repair in PD. These findings hold a promise in devetoping therapies that target Wnt/β-catenin signaling to enhance endogenous restoration and neuronal outcome in age-dependent diseases, such as PD.
