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1.
The molecular mechanisms underlying the induction and maintenance of memory are highly dynamic and comprise distinct phases covering a time window from seconds to even a lifetime. Neuronal networks, which contribute to these processes, have been extensively characterized on various levels of analysis, and imaging techniques allow monitoring of both gross brain activity as well as functional changes in defined brain areas during the time course of memory formation. New techniques developed in honeybees and fruit flies even allow for manipulation of neuronal networks and molecular cascades in a short temporal domain while a living animal under observation acquires new associative memories. These advantages make honeybees and flies ideal organisms to study transient molecular events underlying dynamic memory processing in vivo. In this review we will focus on the temporal features of molecular processes in learning and memory formation, summarize recent knowledge and present an outlook on future developments. 相似文献
2.
Evidence from systems as diverse as mollusks, insects and mammals has revealed that adenylyl cyclase, cyclic adenosine 3′,5′-monophosphate
(cAMP) cascade, cAMP-dependent protein kinases and their substrates are required for the cellular events underlying the short-term
and long-term forms of memory. In Aplysia and Drosophila models, the coincident activation of independent paths converge to produce a synergistic activation of Ca2+/calmodulin-stimulable adenylyl cyclase, thereby enhancing the cAMP level that appears as the primary mediator of downstream
events that strengthen enduring memory. In mammals, in which long-term memories require hippocampal function, our understanding
of the role of adenylyl cyclases is still fragmentary. Of the differently regulated isoforms present in the hippocampus, the
susceptibility of type 1 and type 8 to stimulation by the complex Ca2+/calmodulin and their expression in the hippocampus suggest a role for these two isoforms as a molecular coincidence device
for hippocampus-related memory function. Here, we review the key features of Ca2+/calmodulin stimulable adenylyl cyclases, as well as the involvement of cAMP-regulated signaling pathway in the processes
of learning and memory. 相似文献
3.
Karen Thulasi Devendrakumar Xin Li Yuelin Zhang 《Cellular and molecular life sciences : CMLS》2018,75(16):2981-2989
In plants, mitogen-activated protein kinase (MAPK) cascades are involved in regulating many biological processes including immunity. They relay signals from membrane-residing immune receptors to downstream components for defense activation. Arabidopsis MPK3/6 and MPK4 are activated in two parallel MAPK cascades during PAMP-triggered immunity. MPK3/6 have been implicated in the activation of various immune responses and their inactivation leads to compromised defense against pathogens. On the other hand, the MEKK1-MKK1/2-MPK4 cascade plays critical roles in basal resistance. Disruption of this MAPK cascade results in constitutive defense responses mediated by the NB-LRR protein SUMM2. Interestingly, SUMM2 guards the MEKK1-MKK1/2-MPK4 cascade activity indirectly through monitoring the phosphorylation status of CRCK3, which is a substrate of MPK4. From the pathogens’ side, a number of effectors are shown to target various components of MAPK cascades in plants. Inactivation of MPK4 by the Pseudomonas effector HopAI1 triggers SUMM2-mediated immunity. Together, these findings suggest intricate interplays between PAMP-triggered immunity and effector-triggered immunity via MAPK signaling. 相似文献
4.
On a cellular level, formation of memory is based on a selective change in synaptic efficacy that is both fast and, in case
of important information, long-lasting. Rapidity of cellular changes is achieved by modifying preexisting synaptic molecules
(receptors, ion channels), which instantaneously alters the efficacy of synaptic transmission. Endurance, that is the formation
of long-term memory (LTM), is based on transient and perhaps also long-lasting changes in protein synthesis. A number of different
methods exist to interfere with the synthesis of specific proteins or proteins in general. Other methods, in turn, help to
identify proteins whose synthesis is changed following learning. These mostly molecular methods are briefly described in the
present review. Their successful application in a variety of memory paradigms in invertebrates and vertebrates is illustrated.
The data support the importance of selective changes in gene expression for LTM. Proteins newly synthesized during memory
consolidation are likely to contribute to restructuring processes at the synapse, altering the efficiency of transmission
beyond the scope of STM. Increased or, less often, decreased synthesis of proteins appears during specific time windows following
learning. Recent evidence supports older data suggesting that two or even more waves of protein synthesis exist during the
consolidation period. It is expected that the new molecular methods will help to identify and characterize molecules whose
expression changes during LTM formation even in complex vertebrate learning paradigms. 相似文献
5.
Nhat-Tu Le Uday G. Sandhu Raymundo A. Quintana-Quezada Nguyet Minh Hoang Keigi Fujiwara Jun-ichi Abe 《Cellular and molecular life sciences : CMLS》2017,74(10):1835-1858
Atherosclerosis rarely develops in the region of arteries exposed to undisturbed flow (u-flow, unidirectional flow). Instead, atherogenesis occurs in the area exposed to disturbed flow (d-flow, multidirectional flow). Based on these general pathohistological observations, u-flow is considered to be athero-protective, while d-flow is atherogenic. The fact that u-flow and d-flow induce such clearly different biological responses in the wall of large arteries indicates that these two types of flow activate each distinct intracellular signaling cascade in vascular endothelial cells (ECs), which are directly exposed to blood flow. The ability of ECs to differentially respond to the two types of flow provides an opportunity to identify molecular events that lead to endothelial dysfunction and atherosclerosis. In this review, we will focus on various molecular events, which are differentially regulated by these two flow types. We will discuss how various kinases, ER stress, inflammasome, SUMOylation, and DNA methylation play roles in the differential flow response, endothelial dysfunction, and atherosclerosis. We will also discuss the interplay among the molecular events and how they coordinately regulate flow-dependent signaling and cellular responses. It is hoped that clear understanding of the way how the two flow types beget each unique phenotype in ECs will lead us to possible points of intervention against endothelial dysfunction and cardiovascular diseases. 相似文献
6.
Trefoil factors 总被引:4,自引:0,他引:4
7.
8.
Immunoglobulin light chains are the precursor proteins for fibrils that are formed during primary amyloidosis and in amyloidosis associated with multiple myeloma. As found for the approximately 20 currently described forms of focal, localized, or systemic amyloidoses, light chain-related fibrils extracted from physiological deposits are invariably associated with glycosaminoglycans, predominantly heparan sulfate. Other amyloid-related proteins are either structurally normal, such as beta2-microglobulin and islet amyloid polypeptide, fragments of normal proteins such as serum amyloid A protein or the precursor protein of the beta peptide involved in Alzheimer's disease, or are inherited forms of single amino acid variants of a normal protein such as found in the familial forms of amyloid associated with transthyretin. In contrast, the primary structures of light chains involved in fibril formation exhibit extensive mutational diversity rendering some proteins highly amyloidogenic and others non-pathological. The interactions between light chains and glycosaminoglycans are also affected by amino acid variation and may influence the clinical course of disease by enhancing fibril stability and contributing to resistance to protease degradation. Relatively little is currently known about the mechanisms by which glycosaminoglycans interact with light chains and light-chain fibrils. It is probable that future studies of this uniquely diverse family of proteins will continue to shed light on the processes of amyloidosis, and contribute as well to a greater understanding of the normal physiological roles of glycosaminoglycans. 相似文献
9.
Metastasis: cell-autonomous mechanisms versus contributions by the tumor microenvironment 总被引:12,自引:0,他引:12
The fatality of cancer predominantly results from the dissemination of primary tumor cells to distant sites and the subsequent
formation of metastases. During tumor progression, some of the primary tumor cells as well as the tumor microenvironment undergo
characteristic molecular changes, which are essential for the metastatic dissemination of tumor cells. In this review, we
will discuss recent insights into pro-metastatic events occurring in tumor cells themselves and in the tumor stroma. Tumor
cell-intrinsic alterations include the loss of cell polarity and alterations in cell-cell and cell-matrix adhesion as well
as deregulated receptor kinase signaling, which together support detachment, migration and invasion of tumor cells. On the
other hand, the tumor stroma, including endothelial cells, fibroblasts and cells of the immune system, is engaged in an active
molecular crosstalk within the tumor microenvironment. Subsequent activation of blood vessel and lymph vessel angiogenesis
together with inflammatory and immune-suppressive responses further promotes cancer cell migration and invasion, as well as
initiation of the metastatic process.
Received 4 July 2005; received after revision 3 November 2005; accepted 14 November 2005 相似文献
10.
Over the last two decades the molecular and cellular mechanisms underlying T cell activation, expansion, differentiation,
and memory formation have been intensively investigated. These studies revealed that the generation of memory T cells is critically
impacted by a number of factors, including the magnitude of the inflammatory response and cytokine production, the type of
dendritic cell [DC] that presents the pathogen derived antigen, their maturation status, and the concomitant provision of
costimulation. Nevertheless, the primary stimulus leading to T cell activation is generated through the T cell receptor [TCR]
following its engagement with a peptide MHC ligand [pMHC]. The purpose of this review is to highlight classical and recent
findings on how antigen recognition, the degree of TCR stimulation, and intracellular signal transduction pathways impact
the formation of effector and memory T cells. 相似文献
11.
Protein kinases: which one is the memory molecule? 总被引:12,自引:0,他引:12
Encoding of new experiences is likely to induce activity-dependent modifications in the brain. Studies in organisms far apart
on the phylogenetic scale have shown that similar, sometimes identical, signal transduction pathways subserve plasticity in
neuronal systems, and they may play pivotal roles in the formation of long-term memories. It has become evident that phosphorylation/dephosphorylation
reactions are critical for the initiation of cellular mechanisms that embody, retain and modify information in neural circuits.
Although physiological investigations on synaptic plasticity have had a major impact, we have concentrated our review on behavioural
studies that provide direct or indirect evidence for a role of kinases in mechanisms underlying memory formation. From these,
it appears that the learning event induces activation of a variety of kinases with specific time courses. For instance, the
calcium/calmodulin-dependent protein kinase II seems to participate in an early phase of memory formation. Apparently, activation
of both protein tyrosine kinases and mitogen-activated protein kinases is required for much longer and may thus have a particular
function during transformation from short-term into long-term memory. Quite different time courses appear for protein kinase
C (PKC) and protein kinase A (PKA), which may function at two different time points, shortly after training and again much
later. This suggests that PKC and PKA might play a role at early and late stages of memory formation. However, we have considered
some examples showing that these signalling pathways do not function in isolation but rather interact in an intricate intracellular
network. This is indicative of a more complex contribution of each kinase to the fine tuning of encoding and information processing.
To decipher this complexity, pharmacological, biochemical and genetic investigations are more than ever necessary to unravel
the role of each kinase in the syntax of learning and memory formation. 相似文献
12.
13.
Larsson LI 《Cellular and molecular life sciences : CMLS》2004,61(19-20):2624-2631
Binding of growth factors to cell surface receptors activates protein tyrosine kinases (PTKs) that initiate cascades of downstream signaling events including the mitogen-activated protein (MAP) kinase cascade. This study reports that the PTK inhibitor AG 879 inhibits proliferation of human breast cancer cells through an effect involving inhibition of MAP kinase activation, but which cannot be explained by effects of AG 879 on its known PTK targets. Instead, AG 879 markedly inhibits expression of the RAF-1 gene, which encodes an upstream MAP kinase kinase kinase. Additionally, expression of HER-2, but not of other genes tested, is inhibited by this compound. These novel effects have to be considered when using AG 879 as a TRK-A and HER-2 inhibitor but may have useful therapeutic implications. 相似文献
14.
G. Riedel 《Cellular and molecular life sciences : CMLS》1999,55(4):549-553
Previous work has provided conclusive support for a role of various protein kinases in processes underlying learning and
memory formation. While these processes are not yet established in full detail, it is interesting to entertain the idea of
protein phosphatases being involved in such mechanisms as well. Recent advances in this respect have provided preliminary
support of this view. From the pharmacological as well as the transgenic analysis, it appears that especially the calcineurin/inhibitor-1
cascade plays an important role in the transition of intermediate-term into long-term memory formation. 相似文献
15.
Chunzhang Yang Shervin Rahimpour Albert C. H. Yu Russell R. Lonser Zhengping Zhuang 《Cellular and molecular life sciences : CMLS》2013,70(22):4201-4211
Astrocytic activation is a cellular response to disturbances of the central nervous system (CNS). Recent advances in cellular and molecular biology have demonstrated the remarkable changes in molecular signaling, morphology, and metabolism that occur during astrocyte activation. Based on these studies, it has become clear that the astrocyte activation process is regulated by a variety of signaling pathways, which result in metabolic support, wound healing and scar formation. While normal astrocyte activation pathways drive homeostasis and/or repair in the CNS, dysregulation of these pathways can lead to astrocyte abnormalities, including glioma formation with similar phenotypes as reactive astrocytes. We review the principle pathways responsible for astrocytic activation, as well as their potential contribution to tumor formation in the CNS. 相似文献
16.
Tranguch S Daikoku T Guo Y Wang H Dey SK 《Cellular and molecular life sciences : CMLS》2005,62(17):1964-1973
17.
针对P2P网络中诸如诋毁、合谋、欺骗等安全性问题,提出一种新的基于双信任信息的分布式信任模型。区别对待节点提供服务和发送评价的能力,对节点拥有的资源进行分类;通过迭代求解,为每个节点的每类资源分别计算全局服务信任值和回馈信任值;为了防止恶意节点反复实施恶意行为,引入了惩罚机制,激励节点诚信交易。仿真实验表明,该模型能够迅速降低恶意节点的全局信誉值和恶意交易概率,降低了对无过失节点的不公平性。 相似文献
18.
Natural killer (NK) cells are innate lymphocytes involved in immunosurveillance through their cytotoxic activity and their capacity to secrete inflammatory cytokines. NK cell activation is necessary to initiate effector functions and results from a complex series of molecular and cellular events. We review here the signals that trigger NK cells and discuss recent findings showing that, besides antigen-presenting cells, T cells can play a central role in the initiation of NK cell activation in lymph nodes. 相似文献
19.
Janssen KP 《Cellular and molecular life sciences : CMLS》2003,60(3):495-506
Cancers of the intestine are amongst the most frequent tumors in the Western countries. They arise through the stepwise, progressive disruption of cellular signalling cascades which control cell proliferation, survival and differentiation. The proto-oncogene K-ras functions as an important molecular switch linking several of these signalling pathways. Activating mutations of K-ras are found in about 50% of colorectal cancers, but their contribution to tumor initiation and progression is still poorly understood. Murine models provide excellent opportunities to identify and define the roles of genes involved in cancer formation and growth in the digestive tract. In this review, I will discuss the biological properties of oncogenic K-ras, its influence on cell signalling and its role in colorectal tumorigenesis based on recently established murine models. 相似文献