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1.
T. Hubert S. Grimal P. Carroll A. Fichard-Carroll 《Cellular and molecular life sciences : CMLS》2009,66(7):1223-1238
Collagens are extracellular proteins characterized by a structure in triple helices. There are 28 collagen types which differ
in size, structure and function. Their architectural and functional roles in connective tissues have been widely assessed.
In the nervous system, collagens are rare in the vicinity of the neuronal soma, occupying mostly a “marginal” position, such
as the meninges, the basement membranes and the sensory end organs. In neural development, however, where various ECM molecules
are known to be determinant, recent studies indicate that collagens are no exception, participating in axonal guidance, synaptogenesis
and Schwann cell differentiation. Insights on collagens function in the brain have also been derived from neural pathophysiological
conditions. This review summarizes the significant advances which underscore the function and importance of collagens in the
nervous system.
Received 09 September 2008; received after revision 24 October 2008; accepted 28 October 2008 相似文献
2.
Suzuki Y 《Cellular and molecular life sciences : CMLS》2008,65(3):351-353
We have proposed a chemical chaperone therapy for lysosomal diseases, based on a paradoxical phenomenon that an exogenous
competitive inhibitor of low molecular weight stabilizes the target mutant molecule and restores its catalytic activity as
a molecular chaperone intracellularly. After Fabry disease experiments, we investigated a new synthetic chaperone compound
N-octyl-4-epi-β-valienamine (NOEV) in a GM1-gangliosidosis model mice. Orally administered NOEV entered the brain through the blood-brain barrier, enhanced β-galactosidase
activity, reduced the substrate storage, and clinically improved neurological deterioration. We hope that chemical chaperone
therapy will prove useful for some patients with GM1-gangliosidosis and potentially other lysosomal storage diseases with central nervous system involvement.
Received 10 October 2007; received after revision 31 October 2007; accepted 6 November 2007 相似文献
3.
Investigations into mechanisms that restrict the recovery of functions after an injury to the brain or the spinal cord have
led to the discovery of specific neurite growth inhibitory factors in the adult central nervous system (CNS) of mammals. Blocking
their growth-suppressive function resulted in disinhibition of axonal growth, i.e. growth of cultured neurons on inhibitory
CNS tissue in vitro and regeneration of injured axons in vivo. The enhanced regenerative and compensatory fibre growth was often accompanied by a substantial improvement in the functional
recovery after CNS injury. The first clinical studies to assess the therapeutic potential of compounds that neutralize growth
inhibitors or interfere with their downstream signalling are currently in progress. This review discusses recent advances
in the understanding of how the ‘founder molecule’ Nogo-A and other glialderived growth inhibitors restrict the regeneration
and repair of disrupted neuronal circuits, thus limiting the functional recovery after CNS injuries.
Received 5 April 2007; received after revision 28 September 2007; accepted 1 October 2007 相似文献
4.
Tsatsanis C Dermitzaki E Venihaki M Chatzaki E Minas V Gravanis A Margioris AN 《Cellular and molecular life sciences : CMLS》2007,64(13):1638-1655
Corticotropin-releasing factor (CRF), also termed corticotropin-releasing hormone (CRH) or corticoliberin, is the major regulator
of the adaptive response to internal or external stresses. An essential component of the adaptation mechanism is the adrenal
gland. CRF regulates adrenal function indirectly through the central nervous system (CNS) via the hypothalamic-pituitary-adrenal
(HPA) axis and via the autonomic nervous system by way of locus coeruleus (LC) in the brain stem. Accumulating evidence suggests
that CRF and its related peptides also affect the adrenals directly, i.e. not through the CNS but from within the adrenal gland where they form paracrine regulatory loops. Indeed, CRF and its related
peptides, the urocortins (UCNs: UCN1, UCN2 and UCN3), their receptors CRF type 1 (CRF1) and 2 (CRF2) as well as the endogenous pseudo-receptor CRF-binding protein (CRF-BP) are all expressed in adrenal cortical, medullary
chromaffin and resident immune cells. The intra-adrenal CRF-based regulatory system is complex and depends on the balance
between the local concentration of CRF ligands and the availability of their receptors.
Received 19 December 2006; received after revision 20 February 2007; accepted 26 March 2007 相似文献
5.
Beside its role as a neurotransmitter in the central nervous system, serotonin appears to be a central physiologic mediator
of many gastrointestinal (GI) functions and a mediator of the brain-gut connection. By acting directly and via modulation
of the enteric nervous system, serotonin has numerous effects on the GI tract. The main gut disturbances in which serotonin
is involved are acute chemotherapy-induced nausea and vomiting, carcinoid syndrome and irritable bowel syndrome. Serotonin
also has mitogenic properties. Platelet-derived serotonin is involved in liver regeneration after partial hepatectomy. In
diseased liver, serotonin may play a crucial role in the progression of hepatic fibrosis and the pathogenesis of steatohepatitis.
Better understanding of the role of the serotonin receptor subtypes and serotonin mechanisms of action in the liver and gut
may open new therapeutic strategies in hepato-gastrointestinal diseases.
Received 15 August 2007; received after revision 1 November 2007; accepted 5 November 2007 相似文献
6.
Cheema U Brown RA Alp B MacRobert AJ 《Cellular and molecular life sciences : CMLS》2008,65(1):177-186
Tissue hypoxia results in rapid angiogenesis in vivo, triggered by angiogenic proteins, including vascular endothelial growth factor (VEGF). Current views of tissue viability
are founded on whether ‘deeper-lying’ cells receive sufficient nutrients and oxygen for normal activity and ultimately survival.
For intact tissues, levels of such essential nutrients are governed by micro-vascular perfusion. However, there have been
few effective quantitatively defined 3D models, which enable testing of the interplay or interdependence of matrix and cell
density, and path diffusion on oxygen consumption in vitro. As a result, concepts on cell vulnerability to low oxygen levels, together with the nature of cellular responses are ill
defined. The present study has adapted a novel, optical fibre-based system for in situ, real-time oxygen monitoring within three-dimensionally-spiralled cellular collagen constructs, which were then unfurled
to enable quantitative, spatial measurements of VEGF production in different parts of the same construct exposed to different
oxygen levels. A VEGF response was elicited by cells exposed to low oxygen levels (20 mmHg), primarily within the construct
core.
Received 3 August 2007; received after revision 24 October 2007; accepted 29 October 2007
An erratum to this article is available at . 相似文献
7.
Enanga B Burchmore RJ Stewart ML Barrett MP 《Cellular and molecular life sciences : CMLS》2002,59(5):845-858
Recent progress in understanding the neuro-pathological mechanisms of sleeping sickness reveals a complex relationship between
the trypanosome parasite that causes this disease and the host nervous system. The pathology of late-stage sleeping sickness,
in which the central nervous system is involved, is complicated and is associated with disturbances in the circadian rhythm
of sleep. The blood-brain barrier, which separates circulating blood from the central nervous system, regulates the flow of
materials to and from the brain. During the course of disease, the integrity of the blood-brain barrier is compromised. Dysfunction
of the nervous system may be exacerbated by factors of trypanosomal origin or by host responses to parasites. Microscopic
examination of cerebrospinal fluid remains the best way to confirm late-stage sleeping sickness, but this necessitates a risky
lumbar puncture. Most drugs, including many trypanocides, do not cross the blood-brain barrier efficiently. Improved diagnostic
and therapeutic approaches are thus urgently required. The latter might benefit from approaches which manipulate the blood-brain
barrier to enhance permeability or to limit drug efflux. This review summarizes our current understanding of the neurological
aspects of sleeping sickness, and envisages new research into blood-brain barrier models that are necessary to understand
the interactions between trypanosomes and drugs active against them within the host nervous system.
Received 10 October 2001; received after revision 29 November 2001; accepted 5 December 2001 相似文献
8.
Smith SS 《Cellular and molecular life sciences : CMLS》2001,58(9):1263-1275
A number of steroid hormones and their metabolites fluctuate in the circulation across the human menstrual cycle. In addition to their classic actions on the hypothalamo-pituitary-gonadal axis, many of these hormones act as 'neuroactive steroids' to alter the function of neurotransmitters, such as GABA, within central nervous system circuits. Clinically, these steroids are important because they have not only acute but also long-term effects, and 'withdrawal' properties. This review discusses the effects of steroids such as 3alpha-OH-5alpha-pregnan-20-one (3alpha,5alpha-THP or allopregnanolone) which alter GABA function in distinct ways dependent upon the time course of exposure, to either enhance or decrease inhibition in the brain. These effects are discussed in light of recent clinical findings which seek to further characterize the steroid milieu which underlies pre-menstrual dysphoria. 相似文献
9.
10.
Jurka J 《Cellular and molecular life sciences : CMLS》2008,65(2):201-204
Multiple remnants of transposable elements preserved in cis-regulatory modules may represent a record of mutations that were critical to the evolution of gene regulation and speciation.
Received 13 August 2007; received after revision 8 October 2007; accepted 23 October 2007 相似文献
11.
Savaskan NE Rocha L Kotter MR Baer A Lubec G van Meeteren LA Kishi Y Aoki J Moolenaar WH Nitsch R Bräuer AU 《Cellular and molecular life sciences : CMLS》2007,64(2):230-243
Autotaxin is a secreted cell motility-stimulating exo-phosphodiesterase with lysophospholipase D activity that generates bioactive
lysophosphatidic acid. Lysophosphatidic acid has been implicated in various neural cell functions such as neurite remodeling,
demyelination, survival and inhibition of axon growth. Here, we report on the in vivo expression of autotaxin in the brain during development and following neurotrauma. We found that autotaxin is expressed in
the proliferating subventricular and choroid plexus epithelium during embryonic development. After birth, autotaxin is mainly
found in white matter areas in the central nervous system. In the adult brain, autotaxin is solely expressed in leptomeningeal
cells and oligodendrocyte precursor cells. Following neurotrauma, autotaxin is strongly up-regulated in reactive astrocytes
adjacent to the lesion. The present study revealed the cellular distribution of autotaxin in the developing and lesioned brain
and implies a function of autotaxin in oligodendrocyte precursor cells and brain injuries.
Received 18 September 2006; received after revision 30 October 2006; accepted 4 December 2006 相似文献
12.
Summary In suckling mice injected with steroids, multiple tumors occurred in the sites where neural crest cells normally are present. It is speculated that the phase of the cell cycle of the neural crest cells may have something to do with its cell surface and cellular phenotypic expression in the system mediated by cyclic AMP. 相似文献
13.
In suckling mice injected with steroids, multiple tumors occurred in the sites where neural crest cells normally are present. It is speculated that the phase of the cell cycle of the neural crest cells may have something to do with its cell surface and cellular phenotypic expression in the system mediated by cyclic AMP. 相似文献
14.
The innate immunity of the central nervous system in chronic pain: The role of Toll-like receptors 总被引:1,自引:0,他引:1
Toll-like receptors (TLRs) are a family of pattern recognition receptors that mediate innate immune responses to stimuli from
pathogens or endogenous signals. Under various pathological conditions, the central nervous system (CNS) mounts a well-organized
innate immune response, in which glial cells, in particular microglia, are activated. Further, the innate immune system has
emerged as a promising target for therapeutic control of development and persistence of chronic pain. Especially, microglial
cells respond to peripheral and central infection, injury, and other stressor signals arriving at the CNS and initiate a CNS
immune activation that might contribute to chronic pain facilitation. In the orchestration of this limited immune reaction,
TLRs on microglia appear to be most relevant in triggering and tailoring microglial activation, which might be a driving force
of chronic pain. New therapeutic approaches targeting the CNS innate immune system may achieve the essential pharmacological
control of chronic pain.
Received 21 November 2006; received after revision 8 January 2007; accepted 7 February 2007 相似文献
15.
Williams AE 《Cellular and molecular life sciences : CMLS》2008,65(4):545-562
MicroRNAs (miRNAs) are a recently discovered family of small regulatory molecules that function by modulating protein production.
There are approximately 500 known mammalian miRNA genes, and each miRNA may regulate hundreds of different protein-coding
genes. Mature miRNAs bind to target mRNAs in a protein complex known as the miRNA-induced silencing complex (miRISC), sometimes
referred to as the miRNP (miRNA-containing ribonucleoprotein particles), where mRNA translation is inhibited or mRNA is degraded.
These actions of miRNAs have been shown to regulate several developmental and physiological processes including stem cell
differentiation, haematopoiesis, cardiac and skeletal muscle development, neurogenesis, insulin secretion, cholesterol metabolism
and the immune response. Furthermore, aberrant expression has been implicated in a number of diseases including cancer and
heart disease. The role of miRNAs in these developmental, physiological and pathological processes will be reviewed.
Received 3 August 2007; received after revision 3 October 2007; accepted 5 October 2007 相似文献
16.
Endoplasmic reticulum stress responses 总被引:7,自引:0,他引:7
Schröder M 《Cellular and molecular life sciences : CMLS》2008,65(6):862-894
In homeostasis, cellular processes are in a dynamic equilibrium. Perturbation of homeostasis causes stress. In this review
I summarize how perturbation of three major functions of the endoplasmic reticulum (ER) in eukaryotic cells–protein folding,
lipid and sterol biosynthesis, and storing intracellular Ca2+ – causes ER stress and activates signaling pathways collectively termed the unfolded protein response (UPR). I discuss how
the UPR reestablishes homeostasis, and summarize our current understanding of how the transition from protective to apoptotic
UPR signaling is controlled, and how the UPR induces inflammatory signaling.
Received 21 August 2007; received after revision 26 October 2007; accepted 29 October 2007 相似文献
17.
Plasticins belong to the dermaseptin superfamily of gene-encoded, membrane-active host defense peptides produced by the skin
of hylid frogs. The plasticins, which are rich in Gly and Leu residues arranged in regular 5-mer motifs GXXXG (where X is
any amino acid residue), have very similar amino acid sequences, hydrophobicities, and amphipathicities but differ markedly
in their net charge, conformational plasticity, and activity spectra. The intrinsic flexibility and structural malleability
of plasticins modulate their ability to bind to and disrupt the membranes of prokaryotic and eukaryotic cells, and/or to reach
intracellular targets, therefore triggering functional versatility. This family of closely related but functionally divergent
peptides constitutes a good model to address the relationships between structural polymorphism, membrane-interacting properties,
and the biological activity of antimicrobial, cell-penetrating, and viral fusion peptides. Plasticins could thus serve as
templates to design potent multifunctional drugs that could act simultaneously against bacterial pathogens and viruses.
Received 26 September 2007; received after revision 22 October 2007; accepted 29 October 2007 相似文献
18.
Yibo Wu Zhuo Lv Yang Yang Guoying Dong Yang Yu Yiqiang Cui Man Tong Liu Wang Zuomin Zhou Hui Zhu Qi Zhou Jiahao Sha 《Cellular and molecular life sciences : CMLS》2014,71(9):1761-1774
Blastomere biopsy is used in preimplantation genetic diagnosis; however, the long-term implications on the offspring are poorly characterized. We previously reported a high risk of memory defects in adult biopsied mice. Here, we assessed nervous function of aged biopsied mice and further investigated the mechanism of neural impairment after biopsy. We found that aged biopsied mice had poorer spatial learning ability, increased neuron degeneration, and altered expression of proteins involved in neural degeneration or dysfunction in the brain compared to aged control mice. Furthermore, the MeDIP assay indicated a genome-wide low methylation in the brains of adult biopsied mice when compared to the controls, and most of the genes containing differentially methylated loci in promoter regions were associated with neural disorders. When we further compared the genomic DNA methylation profiles of 7.5-days postconception (dpc) embryos between the biopsy and control group, we found the whole genome low methylation in the biopsied group, suggesting that blastomere biopsy was an obstacle to de novo methylation during early embryo development. Further analysis on mRNA profiles of 4.5-dpc embryos indicated that reduced expression of de novo methylation genes in biopsied embryos may impact de novo methylation. In conclusion, we demonstrate an abnormal neural development and function in mice generated after blastomere biopsy. The impaired epigenetic reprogramming during early embryo development may be the latent mechanism contributing to the impairment of the nervous system in the biopsied mice, which results in a hypomethylation status in their brains. 相似文献
19.
Kaiser M Wetzel S Kumar K Waldmann H 《Cellular and molecular life sciences : CMLS》2008,65(7-8):1186-1201
Biologically active small molecules represent the basis for chemical biology applications in which small molecules are used
as chemical tools to probe biological processes. In this report, we review two approaches to design and synthesize compound
libraries for biological screenings, i.e., diversity-oriented synthesis (DOS) and biology-oriented synthesis (BIOS).
Received 23 October 2007; received after revision 26 November 2007; accepted 28 November 2007 相似文献
20.
Menkes disease is caused by mutations in the copper-transporting P1B-type ATPase ATP7A. ATP7A has a dual function: it serves to incorporate copper into copper-dependent enzymes, and it maintains
intracellular copper levels by removing excess copper from the cytosol. To accomplish both functions, the protein traffics
between different cellular locations depending on copper levels.The mechanism for sensing the concentration of copper, for
trafficking, as well as the details of the mechanism of copper translocation across the membrane are unknown.
Received 24 September 2007; received after revision 12 October 2007; accepted 17 October 2007 相似文献