神经退行性疾病,老年痴呆症(Alzheimer's disease,AD)、帕金森症(Parkinson'sDisease,PD)和中风(脑卒中)严重危害老年人的身体健康和生活质量。这些疾病的发病机制目前尚不完全清楚,也无有效治疗方法。目前的研究发现,氧化应激...神经退行性疾病,老年痴呆症(Alzheimer's disease,AD)、帕金森症(Parkinson'sDisease,PD)和中风(脑卒中)严重危害老年人的身体健康和生活质量。这些疾病的发病机制目前尚不完全清楚,也无有效治疗方法。目前的研究发现,氧化应激产生的活性氧和NO自由基在诱导细胞的凋亡和导致神经退行性疾病AD、PD和中风方面发挥了重要作用。该文章综述了神经退行性疾病的自由基机理和天然抗氧化剂对这些疾病的预防和治疗作用机理。天然抗氧化剂,如茶多酚,能够防止6-羟多巴胺(6-hydroxydopamine,6-OHDA)诱导的细胞凋亡,保护线粒体功能从而预防6-OHDP诱导大鼠的PD症状;大豆异黄酮和尼古丁作为抗氧化剂可以防止Amyloid-β(Aβ)诱导的海马细胞凋亡和转基因小鼠脑中Aβ的沉积,抑制6-OHDA诱导细胞凋亡过程线粒体细胞色素C释放。在转基因鼠海马CA1区的Aβ斑中,铜、铁浓度比周围神经明显增高,用尼古丁处理明显减少海马CA1区Aβ斑及其周围神经中铜和铁的浓度,尼古丁可以抑制分裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)的激活,核因子-κB(Nuclear factor kappa B,NF-κB)和致癌基因蛋白(Myc codes for a protein that binds to theDNA of other genes,C-Myc)的活化,使一氧化氮合酶和一氧化氮生成下调,尼古丁介导的神经信号通路过程受乙酰胆碱受体(acetylcholine receptor,α7nAChRs)调控。研究还发现山楂黄酮通过抑制活性氧和调节一氧化氮自由基可以预防和治疗中风。这些结果为神经退行性疾病的基础理论研究和临床实践提供了新的思路和实验依据。展开更多
The purpose of this paper is to review current infor-mation about the role of inflammation caused by He-licobacter pylori(H. pylori) infection in neurological diseases such as Parkinson's disease, Alzheimer's ...The purpose of this paper is to review current infor-mation about the role of inflammation caused by He-licobacter pylori(H. pylori) infection in neurological diseases such as Parkinson's disease, Alzheimer's dis-ease, Guillain-Barré syndrome, multiple sclerosis, and other inflammatory diseases including ischemic stroke. Infection with H. pylori usually persists throughout life, resulting in a chronic inflammatory response with local secretion of numerous inflammatory mediators includ-ing chemokines [interleukin(IL)-8, macrophage che-motactic protein, growth-regulated oncogene(GRO)-α, chemokine(C-X-C motif) ligand 1] and cytokines [IL-1β, tumor necrosis factor-α, IL-6, IL-12, interferon-g], which can pass into the circulation and have a systemic effect. The persistence of detectable systemic and lo-cal concentrations of inflammatory mediators is likely to alter the outcome of neurological diseases. These proinflammatory factors can induce brain inflammation and the death of neurons and could eventually be asso-ciated to Parkinson's disease and also may be involved in the development of Alzheimer's disease. However,most neurological diseases are the result of a combina-tion of multiple factors, but the systemic inflammatory response is a common component and determinant in the onset, evolution, and outcome of diseases. How-ever, more studies are needed to allow understanding of the effects and mechanisms by which the inflamma-tory response generated by H. pylori infection affects neurological diseases.展开更多
Oxidative stress and mitochondrial damage have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Oxidati...Oxidative stress and mitochondrial damage have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Oxidative stress is characterized by the overproduction of reactive oxygen species, which can induce mitochondrial DNA mutations, damage the mitochondrial respiratory chain, alter membrane permeability, and influence Ca2＋ homeostasis and mitochondrial defense systems. All these changes are implicated in the development of these neurodegenerative diseases, mediating or amplifying neuronal dysfunction and triggering neurodegeneration. This paper summarizes the contribution of oxidative stress and mitochondrial damage to the onset of neurodegenerative diseases and discusses strategies to modify mitochondrial dysfunction that may be attractive therapeutic interventions for the treatment of various neurodegenerative diseases.展开更多
文摘神经退行性疾病,老年痴呆症(Alzheimer's disease,AD)、帕金森症(Parkinson'sDisease,PD)和中风(脑卒中)严重危害老年人的身体健康和生活质量。这些疾病的发病机制目前尚不完全清楚,也无有效治疗方法。目前的研究发现,氧化应激产生的活性氧和NO自由基在诱导细胞的凋亡和导致神经退行性疾病AD、PD和中风方面发挥了重要作用。该文章综述了神经退行性疾病的自由基机理和天然抗氧化剂对这些疾病的预防和治疗作用机理。天然抗氧化剂,如茶多酚,能够防止6-羟多巴胺(6-hydroxydopamine,6-OHDA)诱导的细胞凋亡,保护线粒体功能从而预防6-OHDP诱导大鼠的PD症状;大豆异黄酮和尼古丁作为抗氧化剂可以防止Amyloid-β(Aβ)诱导的海马细胞凋亡和转基因小鼠脑中Aβ的沉积,抑制6-OHDA诱导细胞凋亡过程线粒体细胞色素C释放。在转基因鼠海马CA1区的Aβ斑中,铜、铁浓度比周围神经明显增高,用尼古丁处理明显减少海马CA1区Aβ斑及其周围神经中铜和铁的浓度,尼古丁可以抑制分裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)的激活,核因子-κB(Nuclear factor kappa B,NF-κB)和致癌基因蛋白(Myc codes for a protein that binds to theDNA of other genes,C-Myc)的活化,使一氧化氮合酶和一氧化氮生成下调,尼古丁介导的神经信号通路过程受乙酰胆碱受体(acetylcholine receptor,α7nAChRs)调控。研究还发现山楂黄酮通过抑制活性氧和调节一氧化氮自由基可以预防和治疗中风。这些结果为神经退行性疾病的基础理论研究和临床实践提供了新的思路和实验依据。
基金Supported by Hospital Infantil de México Federico Gómez,No.HIM/2012/018
文摘The purpose of this paper is to review current infor-mation about the role of inflammation caused by He-licobacter pylori(H. pylori) infection in neurological diseases such as Parkinson's disease, Alzheimer's dis-ease, Guillain-Barré syndrome, multiple sclerosis, and other inflammatory diseases including ischemic stroke. Infection with H. pylori usually persists throughout life, resulting in a chronic inflammatory response with local secretion of numerous inflammatory mediators includ-ing chemokines [interleukin(IL)-8, macrophage che-motactic protein, growth-regulated oncogene(GRO)-α, chemokine(C-X-C motif) ligand 1] and cytokines [IL-1β, tumor necrosis factor-α, IL-6, IL-12, interferon-g], which can pass into the circulation and have a systemic effect. The persistence of detectable systemic and lo-cal concentrations of inflammatory mediators is likely to alter the outcome of neurological diseases. These proinflammatory factors can induce brain inflammation and the death of neurons and could eventually be asso-ciated to Parkinson's disease and also may be involved in the development of Alzheimer's disease. However,most neurological diseases are the result of a combina-tion of multiple factors, but the systemic inflammatory response is a common component and determinant in the onset, evolution, and outcome of diseases. How-ever, more studies are needed to allow understanding of the effects and mechanisms by which the inflamma-tory response generated by H. pylori infection affects neurological diseases.
基金supported by the National Natural Science Foundation of China,No.81274005Medical Science Research,Health Department of Hebei Province,No.20110173,20090588Hebei Education Department Science Foundation,No.2007302
文摘Oxidative stress and mitochondrial damage have been implicated in the pathogenesis of several neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis. Oxidative stress is characterized by the overproduction of reactive oxygen species, which can induce mitochondrial DNA mutations, damage the mitochondrial respiratory chain, alter membrane permeability, and influence Ca2＋ homeostasis and mitochondrial defense systems. All these changes are implicated in the development of these neurodegenerative diseases, mediating or amplifying neuronal dysfunction and triggering neurodegeneration. This paper summarizes the contribution of oxidative stress and mitochondrial damage to the onset of neurodegenerative diseases and discusses strategies to modify mitochondrial dysfunction that may be attractive therapeutic interventions for the treatment of various neurodegenerative diseases.
