梓醇在神经退行性疾病中的神经保护作用研究进展

神经退行性疾病（如阿尔茨海默病和帕金森病）,其病理特征是神经元进行性丧失。神经退行性疾病常见于老年人,且发病率逐年上升,给社会及家庭带来沉重负担。梓醇是一种中草药内提取的活性成分,大量的体内外实验研究已证实,梓醇具有抗炎、抗氧化、抗细胞凋亡、促血管生成及神经保护等多种功能,对神经退行性疾病有显著的防治作用,梓醇可能成为一种较理想的神经退行性疾病治疗药物。因此,该文在此基础上就梓醇在神经退行性疾病的作用机制进行综述。     

NADPH氧化酶在神经退行性疾病中的作用

神经退行性疾病与中枢神经系统内的氧化应激、异常蛋白聚集及炎症反应相关。尽管确切的发病机制目前还不清楚,但研究发现NADHP氧化酶(NOX)在神经退行性疾病的发病过程起了重要的作用,可能成为一个新的药物治疗靶点。因此,本文对NOX进行了概述,并探讨了它与神经退行性疾病之间的关系。     

端粒-端粒酶在神经退行性疾病中的研究进展

神经退行性疾病多以β-淀粉样蛋白（β-amyloid,Aβ）、α-突触核蛋白（α-synuclein,α-syn）作为生物标记物来辅助临床进行诊断。近年来,人们发现染色体末端的端粒能够作为衡量生物衰老程度的指标,并发现端粒长度、端粒酶活性可能作为评估老年神经退行性疾病发病风险、疾病进展、不良预后的血液标记物,但目前相关国内外研究结果并不具有一致性。了解端粒相关生物标记物在年龄相关疾病中的作用,是可以帮助临床医生更好地了解疾病的发生发展机制。现就端粒-端粒酶系统在神经退行性疾病中的最新研究进展综述如下,以介绍端粒长度、端粒酶活性对神经退行性疾病的影响以及潜在作用机制。     

氧化应激与神经退行性疾病

自由基氧化应激损伤学说是近年来研究的热点。对阿尔茨海默病(AD)、帕金森病(PD)、肌萎缩侧索硬化症(ALS)和亨廷顿病(HD)等神经退行性疾病特定的遗传和环境因素的研究表明,自由基增多、脂质过氧化、钙稳态失调、细胞色素C释放,是氧化应激增强的主要原因,最终导致神经元凋亡/死亡的发生。氧化应激的增强可能是这些神经退行性疾病基础。随着对神经元凋亡/死亡机制的认识深入,氧化应激在这些疾病中的地位和作用也受到极大的关注。     

动脉自旋标记在神经退行性疾病中的临床应用

动脉自旋标记法(ASL)是一种无创的利用已磁化标记的动脉血作为内源性对比剂来评估脑血流量(CBF)的磁共振成像技术。既往ASL技术主要在脑血管疾病中获得广泛的应用,近年来,ASL技术在神经退行性疾病中的应用也开始受到人们的重视。随着技术的改进,ASL逐渐成为一种可用于帮助明确诊断和监测病情演变的越来越有前途的工具。本文就ASL在神经退行性病变中应用的研究进展进行阐述。     

ERK蛋白在神经退行性疾病中的研究

神经退行性疾病(neurodegenerative diseases,NDs)是指随着年龄增长逐渐出现的由神经元坏死或功能丧失导致的神经功能障碍,不同病理机制下表现出不同类型的临床病症[1].可能的原因包括蛋白酶体功能障碍、自噬缺陷、氧化应激、线粒体失调、兴奋性毒性和神经炎症等[2].随着人均寿命的增加、医疗环境的改善...     

SH-SY5Y细胞的神经分化与神经退行性疾病

SH-SY5Y细胞来源于人骨髓,是神经母细胞瘤细胞系的亚克隆,其形态、生理、生化功能与人体细胞相似,可转化为神经元样细胞,表现出一系列具有高度指导意义的神经生物学特性,且具有可简单快速地大规模扩增、可重复性、低成本维持、与原代神经元的培养相比没有伦理问题等优势,被广泛运用于神经系统疾病的体外实验研究中。SH-SY5Y细胞可以制备成未分化和分化两种形式,通过多种分化方案可使细胞分化为更接近于人体内成熟的神经元样细胞。不同的分化方案可使SH-SY5Y细胞表达不同的神经元表型,且表现出应用于不同疾病病理生理机制研究的优点和局限性,使其更适合研究神经退行性疾病,例如帕金森病、阿尔茨海默病等。该文就SH-SY5Y细胞的神经分化方法及其在神经退行性疾病实验研究中的应用进行综述。     

雄激素在神经退行性疾病中的神经保护作用

<正>神经退行性疾病(neurodegenerative disease)主要包括阿尔兹海默病(Alzheimer's Disease,AD)、帕金森病(Parkinson'sdisease,PD)和亨丁顿病(Huntington disease,HD),是一种神经细胞渐进性功能异常并最终导致死亡的疾病。在成年男性,雄激素有助于维持脑的正常功能。男性衰老后,血和脑内睾酮水平均明显下降,睾酮耗竭会引起脑等雄激素敏感的组织功能障碍和疾病。研究表明,睾酮缺乏可增加AD的发病率。2006年,研究人员发现,退行性疾病病人存在睾酮缺     

诱导多能干细胞与神经退行性疾病

神经退行性疾病,包括帕金森病、阿尔茨海默病和肌萎缩侧索硬化症等的共同特征是在中枢神经系统的不同部位发生特发性神经元丢失.这些神经元的丢失给病人造成了一系列相应的功能障碍.应用人类胚胎干细胞进行细胞替代治疗曾引起人们很大的兴趣,但是一些伦理学问题阻碍了该研究的发展.通过导入特定的转录因子,体细胞能够被诱导为具有胚胎干细胞...     

外泌体在神经退行性疾病发病中的研究进展

外泌体是一种纳米级双层脂质囊泡,它通过主动分选机制包裹特定细胞内容物,包括多种特异性蛋白质、脂质和核酸,靶向作用于受体细胞,参与细胞间信息交流。研究发现,神经元及神经胶质细胞均可释放外泌体,并参与阿尔兹海默病、帕金森病、肌萎缩侧索硬化等神经系统疾病中细胞间物质传递及信息交流。     

The role of osteopontin in neurodegenerative diseases

Osteopontin (OPN) was shown to be involved in inflammatory and degenerative processes of the nervous system. In multiple sclerosis, the role of OPN has been studied in the inflammatory phase, where it was shown that the protein levels increase during disease relapses. Moreover, it was shown that subjects who carry a genotype associated with decreased protein levels tend to display a benign course. Taken altogether, these findings suggest that OPN may play a detrimental role in multiple sclerosis, at least in the inflammatory phase. In common neurodegenerative diseases, such as Parkinson's and Alzheimer's disease, OPN seems to act as a double-edged sword triggering neuronal toxicity and death in some contexts and functioning as a neuroprotectant in others. The involvement of OPN in several biological pathways and networks calls for more extensive research in order to unravel its role in the different disease phases and its potential as a therapeutic target.     

The role of cannabinoids in neurodegenerative diseases

An understanding of the actions of Cannabis (Marijuana) has evolved from folklore to science over the previous hundred years. This progression was spurred by the discovery of an endogenous cannabinoid system consisting of two receptors and two endogenous ligands. This system appears to be intricately involved in normal physiology, specifically in the control of movement, formation of memories and appetite control. As we are developing an increased understanding of the physiological role of endocannabinoids it is becoming clear that they may be involved in the pathology of several neurological diseases. Furthermore an array of potential therapeutic targets is being determined--including specific cannabinoid agonists and antagonists as well as compounds that interrupt the synthesis, uptake or metabolism of the endocannabinoids. This article reviews the recent progress in understanding the contribution of endocannabinoids to the pathology and therapy of Huntington's disease. Parkinson's disease, schizophrenia and tremor.     

The role of autophagy in neurodegenerative diseases

Autophagy is a process where cytoplasmic components of the cell are transported into the lysosomes and degraded. Autophagy is a complex process that is necessary for the normal functioning of any eukaryotic cell. The neurons are among the cells that are the most sensitive to dysfunction of autophagy. Impaired autophagy at different stages leads to a wide variety of neurodegenerative diseases. In this review, we discuss the stages and underlying molecular mechanisms of autophagy in detail and present the data that concern how impairments at one or more of these stages lead to the development of neurodegenerative diseases. The possibility of applying different therapeutic strategies of autophagy modulation for treatment of neurodegenerative diseases is discussed.     

The role of mitochondria in neurodegenerative diseases

Mitochondria are implicated in several metabolic pathways including cell respiratory processes, apoptosis, and free radical production. Mitochondrial abnormalities have been documented in neurodegenerative diseases, including Alzheimer’s, Parkinson’s, and Huntington’s diseases, and amyotrophic lateral sclerosis. Several studies have demonstrated that mitochondrial impairment plays an important role in the pathogenesis of this group of disorders. In this review, we discuss the role of mitochondria in the main neurodegenerative diseases and review the updated knowledge in this field.     

The genetic causes of neurodegenerative diseases

With the application of molecular genetics, we are now beginning to understand the etiology and the early stages of pathogenesis of the major neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Pick's disease and Progressive Supranuclear Palsy. Surprisingly, these studies are showing that these diseases share pathogenic mechanisms which involve tau or synuclein aggregation. In this article, I review the progress in the molecular genetic analysis of these major neurodegenerative diseases and discuss how they are related to each other.     

The neuropathology of sleep in human neurodegenerative diseases

The neuropathology of human sleep remains an ill-defined issue. The data concerning the main structures of human brain areas involved, or supposed to be implicated, in sleep organisation are reviewed. Five levels of organisation can be schematically recognized: (i) the ascending arousal system, (ii) the non REM and REM systems (iii) regulated by hypothalamic areas, (iv) and the biological clock, (v) modulated by a number of "allostatic" influences. These are briefly described, with emphasis on the location of structures involved in humans, and on the recently revised concepts. Current knowledge on the topography of lesions associated with the main sleep disorders in degenerative diseases is recalled, including REM sleep behavior disorders, restless legs syndrome and periodic leg movements, sleep apneas, insomnia, excessive daily sleepiness, secondary narcolepsy and disturbed sleep-wake rhythms. The lesions of sleep related structures observed in early and late stages of four degenerative diseases are then reviewed. Two synucleinopathies (Lewy lesions associated disorders, including Parkinson's disease and Dementia with Lewy bodies, and Multiple System Atrophy) and two tauopathies (Progressive Supranuclear Palsy and Alzheimer's disease) are dealt with. The distribution of lesions usually found in affected patients fit with that expected from the prevalence of different sleep disorders in these diseases. This confirms the current opinion that these disorders depend on the distribution of lesions rather than on their biochemical nature. Further studies might throw insight on the mechanism of normal and pathological sleep in humans, counterpart of the increasing knowledge provided by animal models. Specially designed prospective clinicopathological studies including peculiar attention to sleep are urgently needed.     

Dynamin-related protein 1 and mitochondrial fragmentation in neurodegenerative diseases

The purpose of this article is to review the recent developments of abnormal mitochondrial dynamics, mitochondrial fragmentation, and neuronal damage in neurodegenerative diseases, including Alzheimer's, Parkinson's, Huntington's, and amyotrophic lateral sclerosis. The GTPase family of proteins, including fission proteins, dynamin related protein 1 (Drp1), mitochondrial fission 1 (Fis1), and fusion proteins (Mfn1, Mfn2 and Opa1) are essential to maintain mitochondrial fission and fusion balance, and to provide necessary adenosine triphosphate to neurons. Among these, Drp1 is involved in several important aspects of mitochondria, including shape, size, distribution, remodeling, and maintenance of mitochondria in mammalian cells. In addition, recent advancements in molecular, cellular, electron microscopy, and confocal imaging studies revealed that Drp1 is associated with several cellular functions, including mitochondrial and peroxisomal fragmentation, phosphorylation, SUMOylation, ubiquitination, and cell death. In the last two decades, tremendous progress has been made in researching mitochondrial dynamics, in yeast, worms, and mammalian cells; and this research has provided evidence linking Drp1 to neurodegenerative diseases. Researchers in the neurodegenerative disease field are beginning to recognize the possible involvement of Drp1 in causing mitochondrial fragmentation and abnormal mitochondrial dynamics in neurodegenerative diseases. This article summarizes research findings relating Drp1 to mitochondrial fission and fusion, in yeast, worms, and mammals. Based on findings from the Reddy laboratory and others', we propose that mutant proteins of neurodegenerative diseases, including AD, PD, HD, and ALS, interact with Drp1, activate mitochondrial fission machinery, fragment mitochondria excessively, and impair mitochondrial transport and mitochondrial dynamics, ultimately causing mitochondrial dysfunction and neuronal damage.