microRNAs与骨骼肌疾病

MicroRNA(miRN A)是一类长度约为22个核苷酸的非编码单链RNA分子,它能与mRNA的特定位点结合,参与转录后基因表达调控,从而抑制蛋白质的合成。因此,它在调节基因转录与表达,调控生物体正常发育等各个生理过程中扮演重要角色,同时也对人类疾病的防治以及生物进化探索有着重要意义。有关miRNAs和骨骼肌之间的研究主要集中在miRNAs与骨骼肌生长发育、骨骼肌损伤、骨骼肌疾病。一些普遍表达的miRNAs在胚胎骨骼肌发育和成体骨骼肌再生过程中起着促进作用,且miRNAs调节异常是骨骼肌疾病的一个共同特征。本文主要就miRNAs的生物合成过程和生物学特性,miRNAs在骨骼肌发育过程中的主要功能,以及miRNA对骨骼肌相关疾病的影响和作用作一综述。     

MicroRNA在干细胞增殖与分化过程中的调控作用

背景：研究表明MicroRNA(miRNA)可通过抑制干细胞特定mRNA序列的翻译来调控干细胞的自我更新和分化。 目的：探讨miRNAs在干细胞增殖和分化过程中的作用。 方法：由第一作者检索2000/2010 PubMed数据库、Elsevier数据库及Nature数据库。英文检索词为“stem cell,embryonic stem cell(ESC), induced pluripotent stem cells(iPS cell), microRNA(miRNA)”。排除重复性研究。共保留其中的39篇进行归纳总结。 结果与结论：胚胎干细胞有特异性的miRNAs表达,miRNAs对胚胎干细胞增殖与分化起重要的调控作用;miRNAs对造血干细胞分化的多个阶段和方向有调控作用;miRNAs还参与了神经干细胞、间充质干细胞和皮肤干细胞等成体干细胞分化的调控。干细胞特异性的miRNAs可提高体细胞重编程的效率。     

微小RNA在卵巢中的调控作用

内分泌激素和卵巢内调控因子对正常的卵泡发育和其他的卵巢功能有重要作用。这些调控因素的紊乱可以导致不同的卵巢功能障碍,从而引起不孕、多囊卵巢综合征以及卵巢肿瘤发生。微小RNA(MicroRNA,miRNA)是近年来发现的一种转录后调节因子,本文对正常和病理条件下miRNAs在卵巢中的表达以及潜在的调控功能作一综述,以了解miRNA在卵母细胞的成熟、卵泡发育及卵巢病理中的调控作用。     

MicroRNA与卵巢功能关系的研究进展

微小RNA(microRNAs,miRNAs)是内源性非编码单链小RNA,通过调控靶基因的转录后水平,影响细胞的发育、分化、增殖和凋亡。miRNAs在卵巢的生长发育各阶段中均起着调控作用,还可直接调控卵巢激素的分泌,并在多囊卵巢综合征、卵巢功能早衰、卵巢癌等卵巢疾病中起着重要的调控作用。本文将对目前miRNAs与卵巢发育与功能的相关研究进展进行综述。     

miR-132在神经系统疾病中作用的研究进展

MicroRNAs(miRNAs)作为基因表达的关键调控因子,主要通过在转录后调控大量靶信使RNA(messenger RNA,mRNA)的表达,参与大部分生物学过程以及许多疾病的发病机制。miR-132的表达在神经元发育、成熟过程中是必要的。同时,miR-132作为一种最重要的神经相关miRNAs之一,在神经系统和免疫系统之间起到了关键的调节作用。这表明miR-132在多种疾病的病理进程中扮演了重要角色,尤其在神经系统疾病中。miR-132失调可导致神经发育性疾病,退行性疾病,神经感染以及脑卒中等疾病的发生和发展,现就miR-132在神经系统疾病中发挥的作用及机制进行综述。     

MicroRNA参与喉癌相关基因表达的调控

MicroRNA(miRNA)是一类广泛分布于动植物的非编码小RNA,通过与mRNA互补结合转录后抑制靶基因的表达。研究表明一些miRNAs通过调控肿瘤相关基因表达参与肿瘤的发生、发展,具有癌基因或抑癌基因的相关功能。miRNA在喉癌中存在差异表达,参与喉癌的分子发病机制。     

心肌特异性microRNA在心肌梗死中作用的研究进展

心肌特异性miRNAs,如miR-1、miR-133、miR499和miR208等广泛参与心脏发育和生理病理过程。心肌组织特异性miRNAs不仅参与调控心脏发育早期的心肌分化和后期心肌细胞增殖,同时,心肌特异性miRNAs参与心肌梗死(MI)后的细胞损伤或保护,以及心肌纤维化和心室重构进程;并且能够动员骨髓干细胞入血,促进心肌组织的修复与再生。此外,MI后循环血中心肌特异性miRNAs表达水平明显上调,使其有望成为急性MI早期诊断的确诊指标。     

microRNAs和自身免疫性疾病

microRNAs（miRNAs）是一类进化上保守的微小非编码RNA,通过与靶基因mRNA3’端非翻译区相互作用致使mRNA降解或翻译抑制,在转录后水平调控基因表达,进而影响细胞周期、分化及凋亡等多种细胞生理过程。nfiRNAs在免疫系统的发育及功能行使中具有重要调控作用。研究表明,miRNAs在多种自身免疫性疾病中表达异常,提示miRNAs在自身免疫性疾病的发生发展及防治中具有重大作用。     

脑源性神经营养因子在海马突触联系和可塑性中的作用

脑源性神经营养因子在海马突触的传递和可塑性过程中起重要作用 ,与学习和记忆过程密切相关。它可调节海马神经元突触的基础传递 ,不但在海马早期长时程增强中起作用 ,还参与海马的晚期长时程增强。其作用方式包括突触前调控和突触后调控 ,调节途径包括钙离子及其通道、N 乙酰 D 门冬氨酸受体、丝分裂素相关蛋白激酶和3 磷酸肌醇激酶途径等。     

MicroRNA与脂肪代谢

MicroRNA(miRNA)是一种非编码的小分子RNA,在基因的表达调控过程中起着非常重要的作用.近几年的研究表明,miRNA的表达与人类脂肪组织分布有关,它不但降低脂代谢相关基因的表达,而且抑制脂代谢相关通路(如Wnt通路),并在脂肪细胞的分化以及脂代谢的调节中发挥重要作用.其水平的变化可导致相应的脂质代谢紊乱及肥胖症等疾病的产生,从而可能成为新的药物设计和治疗靶点.     

PSA-NCAM in mammalian structural plasticity and neurogenesis

Polysialic acid (PSA) is a linear homopolymer of alpha2-8-N acetylneuraminic acid whose major carrier in vertebrates is the neural cell adhesion molecule (NCAM). PSA serves as a potent negative regulator of cell interactions via its unusual biophysical properties. PSA on NCAM is developmentally regulated thus playing a prominent role in different forms of neural plasticity spanning from embryonic to adult nervous system, including axonal growth, outgrowth and fasciculation, cell migration, synaptic plasticity, activity-induced plasticity, neuronal-glial plasticity, embryonic and adult neurogenesis. The cellular distribution, developmental changes and possible function(s) of PSA-NCAM in the central nervous system of mammals here are reviewed, along with recent findings and theories about the relationships between NCAM protein and PSA as well as the role of different polysialyltransferases. Particular attention is focused on postnatal/adult neurogenesis, an issue which has been deeply investigated in the last decade as an example of persisting structural plasticity with potential implications for brain repair strategies. Adult neurogenic sites, although harbouring all subsequent steps of cell differentiation, from stem cell division to cell replacement, do not faithfully recapitulate development. After birth, they undergo morphological and molecular modifications allowing structural plasticity to adapt to the non-permissive environment of the mature nervous tissue, that are paralled by changes in the expression of PSA-NCAM. The use of PSA-NCAM as a marker for exploring differences in structural plasticity and neurogenesis among mammalian species is also discussed.     

Epigenetic choreographers of neurogenesis in the adult mammalian brain

Epigenetic mechanisms regulate cell differentiation during embryonic development and also serve as important interfaces between genes and the environment in adulthood. Neurogenesis in adults, which generates functional neural cell types from adult neural stem cells, is dynamically regulated by both intrinsic state-specific cell differentiation cues and extrinsic neural niche signals. Epigenetic regulation by DNA and histone modifiers, non-coding RNAs and other self-sustained mechanisms can lead to relatively long-lasting biological effects and maintain functional neurogenesis throughout life in discrete regions of the mammalian brain. Here, we review recent evidence that epigenetic mechanisms carry out diverse roles in regulating specific aspects of adult neurogenesis and highlight the implications of such epigenetic regulation for neural plasticity and disorders.     

Reelin signaling in development,maintenance, and plasticity of neural networks

The developing brain is formed through an orchestrated pattern of neuronal migration, leading to the formation of heterogeneous functional regions in the adult. Several proteins and pathways have been identified as mediators of developmental neuronal migration and cell positioning. However, these pathways do not cease to be functionally relevant after the embryonic and early postnatal period; instead, they switch from guiding cells, to guiding synapses. The outcome of synaptic guidance determines the strength and plasticity of neuronal networks by creating a scalable functional architecture that is sculpted by cues from the internal and external environment. Reelin is a multifunctional signal that coordinates cortical and subcortical morphogenesis during development and regulates structural plasticity in adulthood and aging. Gain or loss of function in reelin or its receptors has the potential to influence synaptic strength and patterns of connectivity, with consequences for memory and cognition. The current review highlights similarities in the signaling cascades that modulate neuronal positioning during development, and synaptic plasticity in the adult, with a focus on reelin, a glycoprotein that is increasingly recognized for its dual role in the formation and maintenance of neural circuits.     

Spatiotemporal expression patterns of mammalian chordin during postgastrulation embryogenesis and in postnatal brain.

Chordin is an antagonist of TGFbeta-like bone morphogenetic proteins (BMPs) that plays roles in dorsoventral axis formation and in induction, maintenance and/or differentiation of neural tissue in early vertebrate embryogenesis. In contrast, little is known concerning possible roles for Chordin at later stages of vertebrate development and in the adult. To provide insights into possible postgastrulation roles for Chordin, we report the spatiotemporal expression patterns of Chordin in 8.5- to 15.5-dpc mouse embryos and in the postnatal mouse brain. Expression of Chordin in the primordia of most major organs from 10.5 dpc, including the brain, lung, heart, liver, kidney, thymus, and gut, suggests multiple functions for Chordin in organogenesis, potentially by means of interactions with TGFbeta-like BMPs. The relatively high levels of Chordin expression in condensing and differentiating cartilage elements from 11.5 dpc indicates a generalized role for Chordin throughout embryonic skeletogenesis. In the postnatal mouse brain, we demonstrate that Chordin is coexpressed with other components of the TGFbeta-like BMP signalling pathway in the cerebellum and hippocampus, sites of high synaptic plasticity, suggesting a role for Chordin in this process.     

神经黏附分子NB-3在中枢神经系统中的功能

神经黏附分子属于免疫球蛋白超家族，它不仅在发育中与形成轴突生长方向和突触连接有关，而且在成体的突触可塑性和记忆中也发挥重要的作用。NB-3是1996年发现的神经黏附分子，属于免疫球蛋白超家族的Contactin亚家族，集中表达于神经系统。NB-3可促进神经元轴突的生长，参与少突胶质细胞的分化与成熟，促进小脑发育及功能维持。     

Rapid, experience-dependent expression of synaptic NMDA receptors in visual cortex in vivo

Sensory experience is crucial in the refinement of synaptic connections in the brain during development. It has been suggested that some forms of experience-dependent synaptic plasticity in vivo are associated with changes in the complement of postsynaptic glutamate receptors, although direct evidence has been lacking. Here we show that visual experience triggers the rapid synaptic insertion of new NMDA receptors in visual cortex. The new receptors have a higher proportion of NR2A subunits and, as a consequence, different functional properties. This effect of experience requires NMDA receptor activation and protein synthesis. Thus, rapid regulation of postsynaptic glutamate receptors is one mechanism for developmental plasticity in the brain. Changes in NMDA receptor expression provide a mechanism by which brief sensory experience can regulate the properties of NMDA receptor-dependent plasticity in visual cortex.     

Evidence demonstrating role of microRNAs in the etiopathology of major depression

Major depression is a debilitating disease. Despite a tremendous amount of research, the molecular mechanisms associated with the etiopathology of major depression are not clearly understood. Several lines of evidence indicate that depression is associated with altered neuronal and structural plasticity and neurogenesis. MicroRNAs are a newly discovered prominent class of gene expression regulators that have critical roles in neural development, are needed for survival and optimal health of postmitotic neurons, and regulate synaptic functions, particularly by regulating protein synthesis in dendritic spines. In addition, microRNAs (miRNAs) regulate both embryonic and adult neurogenesis. Given that miRNAs are involved in neural plasticity and neurogenesis, the concept that miRNAs may play an important role in psychiatric illnesses, including major depression, is rapidly advancing. Emerging evidence demonstrates that the expression of miRNAs is altered during stress, in the brain of behaviorally depressed animals, and in human postmortem brain of depressed subjects. In this review article, the possibility that dysregulation of miRNAs and/or altered miRNA response may contribute to the etiology and pathophysiology of depressive disorder is discussed.