环状RNA在胶质瘤中的研究进展

环状RNA(circRNA)是一种新型的环状功能性非编码RNA,在真核生物中广泛分布,与传统线性RNA分子相比,没有多聚腺苷酸尾结构,且具有更强的稳定性.circRNA在胶质瘤等多种肿瘤的发生发展进程中发挥重要调节作用,且已用作潜在的生物标志物和肿瘤相关治疗靶点.本文就circRNA的生物学特点、功能以及与神经胶质瘤相...     

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。     

RNA干扰及其在神经变性性疾病研究中的应用

RNA干扰(RNAi)是指生物体内利用具有同源性的双链RNA(dsRNA)诱发序列特异的转录后基因沉默(PTGS)的现象，它可以通过抑制蛋白表达模拟基因敲除技术。RNAi主要通过dsRNA被核酸酶Dicer切割成21～25nt的小干扰RNA(siRNA)，由siRNA介导识别并靶向切割同源mRNA分子而实现。随着研究的不断深入，RNAi的作用机制将逐步被阐明，其技术也将日趋完善和成熟，并将得到广泛的应用。本文就RNAi技术的研究进展及其在阿尔茨海默病、帕金森病等神经变性性疾病研究中的应用作一综述。     

环状RNA circ_0014359在神经胶质瘤中的表达水平及其临床意义

目的 研究胶质瘤组织的circ_0014359表达水平及其在胶质瘤诊疗中的临床意义.方法 采用qRT-PCR法检测胶质瘤组织及正常脑组织的circ_0014359表达水平.分析circ_0014359表达水平与患者临床病理特征之间的关系.应用生存曲线分析circ_0014359表达与胶质瘤患者预后的关系.用单因素分析和...     

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。     

神经退行性疾病的表观遗传学研究进展

神经退行性疾病,包括阿尔茨海默病(AD)、帕金森病(PD)、肌萎缩侧索硬化症(ALS),等.是一类特定亚型神经元进行性丢失导致功能障碍的疾病.神经退行性疾病目前病因不清,遗传和环境因素均与疾病相关.近年研究表明,表观遗传调控介导了遗传和环境因素的相互作用,主要通过DNA甲基化、组蛋白修饰和非编码RNA的复杂相互作用,从...     

环状RNA circ＿100782在神经胶质瘤中的表达及其临床意义

目的探讨环状RNA circ_100782在神经胶质瘤患者中的表达与神经胶质瘤临床病理特征及预后的关系。方法实时荧光定量聚合酶链反应(qRT-PCR)法检测神经胶质瘤及其正常脑组织中环状RNA circ_100782的表达量。卡方检验(chi-square test)分析环状RNA circ_100782的表达差异与临床资料及病理特征的关系。生存曲线(Kaplan-Meier)分析环状RNA circ_100782的表达差异与临床预后的相关性。Cox比例风险回归模型进行单变量和多变量回归分析。结果环状RNA circ_100782在神经胶质瘤组织中的相对表达水平高于正常脑组织(P0.05)。环状RNA circ_100782高表达与WHO分级(P=0.003)密切相关。生存曲线(Kaplan-Meier)分析显示,环状RNA circ_100782高表达患者与环状RNA circ_100782低表达患者相比,总体存活率显著较低(P=0.0291),单变量Cox比例风险回归模型分析显示,环状RNA circ_100782表达水平和WHO分级与神经胶质瘤患者的总生存率相关(均P0.05)。多变量分析确定环状RNA circ_100782为神经胶质瘤独立预后因素。结论环状RNA circ_100782高表达与神经胶质瘤预后相关。因此,环状RNA circ_100782可以作为预测神经胶质瘤患者预后的潜在生物标志物。     

脑膜淋巴系统在神经疾病中的作用及机制的研究进展

脑膜淋巴管系统的发现更新了对中枢神经系统（CNS）淋巴引流和免疫应答的传统认知。文章对脑膜淋巴管系统的解剖、生长发育、衰老和生理功能以及其在阿尔茨海默病（AD）、帕金森病（PD）、多发性硬化（MS）和CNS感染性疾病等多种神经疾病中的作用机制的最新研究进展进行综述，为进一步理解脑膜淋巴管系统在这些疾病中的作用机制，开发靶向脑膜淋巴管系统的防治方法提供理论依据。     

癫痫中环状RNA的研究现状

癫痫是一种神经系统慢性疾病,给家庭和社会带来沉重的经济及照护负担,其发病机制复杂,且约1/3的癫痫患者对药物治疗不敏感,发现一种可以诊断及治疗的分子标志物势在必行。近年来人们对环状RNA(circular RNA,circRNA)的研究越来越多,其作为非编码RNA的重要成员,可作为调控工具、生物标志物、治疗靶点,分别为癫痫的病理生理研究、诊断、治疗提供新的指导和方向。本综述结合国内外相关报道,旨在阐述circRNA相关功能、特性及其与癫痫相关性,为进一步研究circRNA与癫痫提供理论依据。     

环状RNA circ-0014359在胶质瘤组织中的表达及意义

目的 探讨环状RNA circ-0014359（简称circ-0014359）在胶质瘤组织中的表达及意义。方法 实时定量PCR法检测118例胶质瘤组织和60例正常脑组织circ-0014359的表达水平。以circ-0014359表达量中位数为截断值,分为高表达和低表达。随访结束时间为2019年6月,总生存期（OS）为术后第1天至死亡或最后一次随访,无进展生存期（PFS）为术后至第一次发生疾病进展或任何原因死亡的时间。结果 胶质瘤组织circ-0014359表达水平明显高于正常脑组织（P<0.05）。随胶质瘤病理级别增高,circ-0014359表达水平明显增高（P<0.05）。多因素Cox比例回归风险模型分析结果显示,circ-0014359高表达是胶质瘤病人OS和PFS较短的独立影响因素（P<0.05）。生存曲线分析显示,高表达组OS和PFS[分别为（25.31±8.03）个月和（15.22±3.13）个月]明显低于低表达组[分别为（35.19±7.03）个月和（19.32±2.84）个月;P<0.05]。结论 胶质瘤组织circ-0014359呈高表达,并且与不良预后有关。     

Potential role of viruses in neurodegeneration

Viruses have the capacity to induce alterations and degenerations of neurons by different direct and indirect mechanisms. In the review, we have focused on some examples that may provide new avenues for treatment or altering the course of infections, i.e., antibodies to fusogenic virus membrane proteins, drugs that interfere with lipid metabolism, calcium channel blockers, immunoregulatory molecules, and, and inhibitors of excitotoxic amino acids. Owing to their selectivity in attack on regions of nervous tissue, governed by viral factors and by routes of invasion, viral receptors or metabolic machineries of infected cells, certain viral infections show similarities in distribution of their resulting lesions in the nervous system to that of the common human neurodegenerative diseases (namely, motor neurons disease, Parkinson’s disease, and Alzheimer’s disease). However, it should be emphasized that no infectious agent has as yet provided a complete animal model for any of these diseases, nor has any infectious agent been linked to them from observations on clinical or postomortem materials.     

The role of excitotoxicity in neurodegeneration

A body of evidence suggests that the mechanisms of excitotoxic neuronal damage evoked by excessive or prolonged activation of the excitatory amino acid receptors may be involved in pathogenesis of brain damage in acute insults and in chronic neurodegenerative diseases. In this review we briefly discuss several selected mechanisms of the excitotoxicity, focusing attention on the role of ionotropic glutamate receptors, calcium transients and calcium-mediated cell injury. In the second part of this paper we provide information on elements of excitotoxicity in brain diseases.     

泛酸激酶相关性神经变性疾病遗传学与临床研究进展

泛酸激酶相关性神经变性疾病是脑组织铁沉积性神经变性(NBIA,曾称为Hallervorden-Spatz综合征)疾病的主要发病类型之一,系由泛酸激酶2(PANK2)基因突变所导致的常染色体隐性遗传性疾病。PANK2基因突变可干扰PANK2蛋白表达水平和催化活性,以及线粒体靶蛋白的成熟与稳定性,引起神经元线粒体脂类代谢异常改变,导致脑组织铁沉积性神经变性疾病。本文对该病分子遗传学机制及其与临床表型和影像学特征相关的研究成果和进展进行概述。     

Melanin affinity and its possible role in neurodegeneration

Certain drugs with melanin affinity are known to have caused pigmentary lesions in the eye and skin. This was the basis for the hypothesis that compounds with melanin affinity may cause damage also in other melanin-bearing tissues such as the substantia nigra. The heterogeneity of compounds that binds to melanin is large. Toxins, drugs, and several other compounds have melanin affinity. Compounds showing the highest affinity are mainly organic amines and metal ions. The binding of toxicants to melanin probably protects the cells initially. However, the binding is normally, slowly reversible and melanin may accumulate the toxicant and gradually release it into the cytosol. Several studies indicate that neuromelanin may play a significant role both in the initiation and in the progression of neurodegeneration. MPTP/MPP⁺ that has been causally linked with Parkinsonism has high affinity for neuromelanin, and the induced dopaminergic denervation correlates with the neuromelanin content in the cells. This shows that the toxicological implications of the accumulation of toxicants in pigmented neurons and its possible role in neurodegeneration should not be neglected. Extracellular neuromelanin has been reported to activate dendritic cells and microglia. An initial neuronal damage induced by a neurotoxicant that leaks neuromelanin from the cells may therefore lead to a vicious cycle of neuroinflammation and further neurodegeneration. Although there are many clues to the particular vulnerability of dopaminergic neurons of substantia nigra in Parkinson’s disease, the critical factors are not known. Further studies to determine the importance of neuromelanin in neurodegeneration and Parkinson’s disease are warranted.     

Statins: the role in the treatment and prevention of Alzheimer's neurodegeneration

Alzheimer's disease (AD) is a progressive neurodegenerative disease commonly seen in the elderly and is characterized by progressive cognitive and physical decline. Current understanding of AD pathogenesis revolves around amyloid-β peptide (Aβ), a product of the sequential proteolytic cleavage of the transmembrane amyloid-β protein precursor (AβPP) by β- and γ-secretase, enzymes found predominantly in the cholesterol rich micro domains of the cell membrane. Several risk factors for AD are associated with cholesterol metabolism, including dyslipidaemia, coronary artery and cerebrovascular disease. Statins are widely prescribed for their cholesterol lowering ability and show a favorable side effect profile overall. By competitive inhibition of hydroxymethyl co-enzyme A-reductase, statins reduce the production of cholesterol and isoprenoid intermediates including geranylgeranyl and farnesyl pyrophosphate. These isoprenoids modify recently translated proteins such as small GTPase molecules that are essential in numerous cell-signaling pathways, including vesicular trafficking and inflammation. In experimental models of AD, statins reduce the production of Aβ by disrupting secretase enzyme function and by reducing neuroinflammation. Furthermore, epidemiological studies suggest that statins may reduce the incidence of AD. Consequently, statins, secondary of their anti-hypercholesterolaemic, plieotropic and anti-inflammatory effects, are being investigated for a potential therapeutic role. This review will discuss evidence for the role of statins in the treatment and prevention of AD neurodegeneration.     

Advances in imaging angiogenesis and inflammation in atherosclerosis

Advances in imaging technology have provided powerful tools for dissecting the angiogenic and inflammatory aspects of atherosclerosis. Improved technology along with multi-modal approaches has expanded the utilisation of imaging. Recent advances provide the ability to better define structure and development of angiogenic vessels, identify relationships between inflammatory mediators and the vessel wall, validate biological effects of anti-inflammatory and anti-angiogenic drugs, delivery and/or targeting specific molecules to inflammatory regions of atherosclerotic plaques.     

Mechanistic role of calpains in postischemic neurodegeneration.

The calpain family of proteases is causally linked to postischemic neurodegeneration. However, the precise mechanisms by which calpains contribute to postischemic neuronal death have not been fully elucidated. This review outlines the key features of the calpain system, and the evidence for its causal role in postischemic neuronal pathology. Furthermore, the consequences of specific calpain substrate cleavage at various subcellular locations are explored. Calpain substrates within synapses, plasma membrane, endoplasmic reticulum, lysosomes, mitochondria, and the nucleus, as well as the overall effect of postischemic calpain activity on calcium regulation and cell death signaling are considered. Finally, potential pathways for calpain-mediated neurodegeneration are outlined in an effort to guide future studies aimed at understanding the downstream pathology of postischemic calpain activity and identifying optimal therapeutic strategies.