共查询到20条相似文献,搜索用时 15 毫秒
1.
Leah Zuroff David Daley Keith L. Black Maya Koronyo-Hamaoui 《Cellular and molecular life sciences : CMLS》2017,74(12):2167-2201
Deficiency in cerebral amyloid β-protein (Aβ) clearance is implicated in the pathogenesis of the common late-onset forms of Alzheimer’s disease (AD). Accumulation of misfolded Aβ in the brain is believed to be a net result of imbalance between its production and removal. This in turn may trigger neuroinflammation, progressive synaptic loss, and ultimately cognitive decline. Clearance of cerebral Aβ is a complex process mediated by various systems and cell types, including vascular transport across the blood–brain barrier, glymphatic drainage, and engulfment and degradation by resident microglia and infiltrating innate immune cells. Recent studies have highlighted a new, unexpected role for peripheral monocytes and macrophages in restricting cerebral Aβ fibrils, and possibly soluble oligomers. In AD transgenic (ADtg) mice, monocyte ablation or inhibition of their migration into the brain exacerbated Aβ pathology, while blood enrichment with monocytes and their increased recruitment to plaque lesion sites greatly diminished Aβ burden. Profound neuroprotective effects in ADtg mice were further achieved through increased cerebral recruitment of myelomonocytes overexpressing Aβ-degrading enzymes. This review summarizes the literature on cellular and molecular mechanisms of cerebral Aβ clearance with an emphasis on the role of peripheral monocytes and macrophages in Aβ removal. 相似文献
2.
Differential roles of multiple adhesion molecules in cell migration: granule cell migration in cerebellum 总被引:2,自引:0,他引:2
C M Chuong 《Experientia》1990,46(9):892-899
The migration of cerebellar granule cells from the external granular layer to the internal granular layer is mediated by the radical Bergmann glial fiber. Recent works have shown that cell adhesion molecules, extra-cellular matrix proteins and proteolytic enzymes or their activators are involved in this process. Immuno-localization studies showed differential temporal and spatial expression patterns of different adhesion molecules, their isoforms, and post-translational modification during different stages of granule cell migration. Functional perturbation experiments using cerebellar explant cultures demonstrated that several adhesion molecules as well as plasminogen activator are involved in granule cell migration and are required in different stages. Other systems used to study granule cell migration including dissociated microwell cultures and granule cell deficient mouse mutants are discussed in the context of adhesion molecules. The results accumulated so far suggest that the migration of granule cells is a complex process in which the cooperation of a group of molecules with different functions, some for adhesion some for de-adhesion, are required to fulfill the different needs during the migratory course. 相似文献
3.
C. -M. Chuong 《Cellular and molecular life sciences : CMLS》1990,46(9):892-899
Summary The migration of cerebellar granule cells from the external granular layer to the internal granular layer is mediated by the radial Bergmann glial fiber. Recent works have shown that cell adhesion molecules, extra-cellular matrix proteins and proteolytic enzymes or their activators are involved in this process. Immuno-localization studies showed differential temporal and spatial expression patterns of different adhesion molecules, their isoforms, and post-translational modification during different stages of granule cell migration. Functional perturbation experiments using cerebellar explant cultures demonstrated that several adhesion molecules as well as plasminogen activator are involved in granule cell migration and are required in different stages. Other systems used to study granule cell migration including dissociated microwell cultures and granule cell deficient mouse mutants are discussed in the context of adhesion molecules. The results accumulated so far suggest that the migration of granule cells is a complex process in which the cooperation of a group of molecules with different functions, some for adhesion some for de-adhesion, are required to fulfill the different needs during the migratory course. 相似文献
4.
Selective degradation of cellular proteins serves to eliminate abnormal proteins and to mediate the turnover of certain short-lived proteins, many of which have regulatory functions. In eukaryotes a major pathway for selective protein degradation is ATP-dependent and is mediated by the ubiquitin system. This pathway involves substrate recognition by components of a ubiquitin-protein ligase system, covalent attachment of ubiquitin moieties to proteolytic substrates, and subsequent degradation of these conjugates by a multicatalytic protease complex. Recent genetic evidence suggests that the remarkable selectivity of this process is largely controlled at the level of substrate recognition by the ubiquitin ligase system. In Saccharomyces cerevisiae, ubiquitin-conjugating enzymes UBC1, UBC4 and UBC5 have been identified as key components of this highly conserved degradation pathway. Genetic analysis indicates that ubiquitin-dependent proteolysis is essential for cell viability and that UBC4 and UBC5 enzymes are essential components of the eukaryotic stress response. 相似文献
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Selective degradation of cellular proteins serves to eliminate abnormal proteins and to mediate the turnover of certain short-lived proteins, many of which have regulatory functions. In eukaryotes a major pathway for selective protein degradation is ATP-dependent and is mediated by the ubiquitin system. This pathway involves substrate recognition by components of a ubiquitin-protein ligase system, covalent attachment of ubiquitin moieties to proteolytic substrates, and subsequent degradation of these conjugates by a multicatalytic protease complex. Recent genetic evidence suggests that the remarkable selectivity of this process is largely controlled at the level of substrate recognition by the ubiquitin ligase system. InSaccharomyces cerevisiae, ubiquitin-conjugating enzymes UBC1, UBC4 and UBC5 have been identified as key components of this highly conserved degradation pathway. Genetic analysis indicates that ubiquitin-dependent proteolysis is essential for cell viability and that UBC4 and UBC5 enzymes are essential components of the eukaryotic stress response. 相似文献
7.
Alexey A. Tinkov Geir Bjørklund Anatoly V. Skalny Margarita G. Skalnaya Salvatore Chirumbolo Jan Aaseth 《Cellular and molecular life sciences : CMLS》2018,75(9):1567-1586
Mammalian thioredoxin reductase (TrxR) is a selenoprotein with three existing isoenzymes (TrxR1, TrxR2, and TrxR3), which is found primarily intracellularly but also in extracellular fluids. The main substrate thioredoxin (Trx) is similarly found (as Trx1 and Trx2) in various intracellular compartments, in blood plasma, and is the cell’s major disulfide reductase. Thioredoxin reductase is necessary as a NADPH-dependent reducing agent in biochemical reactions involving Trx. Genetic and environmental factors like selenium status influence the activity of TrxR. Research shows that the Trx/TrxR system plays a significant role in the physiology of the adipose tissue, in carbohydrate metabolism, insulin production and sensitivity, blood pressure regulation, inflammation, chemotactic activity of macrophages, and atherogenesis. Based on recent research, it has been reported that the modulation of the Trx/TrxR system may be considered as a new target in the management of the metabolic syndrome, insulin resistance, and type 2 diabetes, as well as in the treatment of hypertension and atherosclerosis. In this review evidence about a possible role of this system as a marker of the metabolic syndrome is reported. 相似文献
8.
Emilia Pedone Danila Limauro Katia D’Ambrosio Giuseppina De Simone Simonetta Bartolucci 《Cellular and molecular life sciences : CMLS》2010,67(22):3797-3814
The Thioredoxin (Trx) fold is a versatile protein scaffold consisting of a four-stranded β-sheet surrounded by three α-helices.
Various insertions are possible on this structural theme originating different proteins, which show a variety of functions
and specificities. During evolution, the assembly of different Trx fold domains has been used many times to build new multi-domain
proteins able to perform a large number of catalytic functions. To clarify the interaction mode of the different Trx domains
within a multi-domain structure and how their combination can affect catalytic performances, in this review, we report on
a structural and functional analysis of the most representative proteins containing more than one catalytically active Trx
domain: the eukaryotic protein disulfide isomerases (PDIs), the thermophilic protein disulfide oxidoreductases (PDOs) and
the hybrid peroxiredoxins (Prxs). 相似文献
9.
Infection of bacteria triggers innate immune defense reactions in Drosophila. So far, the only bacterial component known to be recognized by the insect innate immune system is peptidoglycan, one of
the most abundant constituents of the bacterial cell wall. Insects use peptidoglycan recognition proteins to detect peptidoglycan
and to activate innate immune responses. Such specialized peptidoglycan receptors appear to have evolved from phage enzymes
that hydrolyze bacterial cell walls. They are able to bind specific peptidoglycan molecules with distinct chemical moieties
and activate innate immune pathways by interacting with other signaling proteins. Recent X-ray crystallographic studies of
the peptidoglycan recognition proteins LCa, and LCx bound to peptidoglycan have provided structural insights into recognition
of peptidoglycan and activation of innate immunity in insects.
Received 28 December 2006; received after revision 2 February 2007; accepted 21 February 2007 相似文献
10.
Calmodulin-dependent cyclic nucleotide phosphodiesterase (PDE1) 总被引:4,自引:0,他引:4
R. Kakkar R. V. S. Raju R. K. Sharma 《Cellular and molecular life sciences : CMLS》1999,55(8-9):1164-1186
11.
Transgenic expression and activation of PGC-1α protect dopaminergic neurons in the MPTP mouse model of Parkinson’s disease 总被引:1,自引:1,他引:0
Mudò G Mäkelä J Di Liberto V Tselykh TV Olivieri M Piepponen P Eriksson O Mälkiä A Bonomo A Kairisalo M Aguirre JA Korhonen L Belluardo N Lindholm D 《Cellular and molecular life sciences : CMLS》2012,69(7):1153-1165
12.
Poly-ADP-ribosylation in health and disease 总被引:6,自引:0,他引:6
13.
Bruno Mesmin Bruno Antonny Guillaume Drin 《Cellular and molecular life sciences : CMLS》2013,70(18):3405-3421
In cells, the levels of sterol vary greatly among organelles. This uneven distribution depends largely on non-vesicular routes of transfer, which are mediated by soluble carriers called lipid-transfer proteins (LTPs). These proteins have a domain with a hydrophobic cavity that accommodates one sterol molecule. However, a demonstration of their role in sterol transport in cells remains difficult. Numerous LTPs also contain membrane-binding elements, but it is not clear how these LTPs couple their ability to target organelles with lipid transport activity. This issue appears critical, since many sterol transporters are thought to act at contact sites between two membrane-bound compartments. Here, we emphasize that biochemical and structural studies provide precious insights into the mode of action of sterol-binding proteins. Recent studies on START, Osh/ORP and NPC proteins suggest models on how these proteins could transport sterol between organelles and, thereby, influence cellular functions. 相似文献
14.
Rosy El Ramy Najat Magroun Nadia Messadecq Laurent R. Gauthier François D. Boussin Ullas Kolthur-Seetharam Valérie Schreiber Michael W. McBurney Paolo Sassone-Corsi Françoise Dantzer 《Cellular and molecular life sciences : CMLS》2009,66(19):3219-3234
Poly(ADP-ribose) polymerase-1 (Parp-1) and the protein deacetylase SirT1 are two of the most effective NAD+-consuming enzymes in the cell with key functions in genome integrity and chromatin-based pathways. Here, we examined the
in vivo crosstalk between both proteins. We observed that the double disruption of both genes in mice tends to increase late
post-natal lethality before weaning consistent with important roles of both proteins in genome integrity during mouse development.
We identified increased spontaneous telomeric abnormalities associated with decreased cell growth in the absence of either
SirT1 or SirT1 and Parp-1 in mouse cells. In contrast, the additional disruption of Parp-1 rescued the abnormal pericentric
heterochromatin, the nucleolar disorganization and the mitotic defects observed in SirT1-deficient cells. Together, these
findings are in favor of key functions of both proteins in cellular response to DNA damage and in the modulation of histone
modifications associated with constitutive heterochromatin integrity. 相似文献
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16.
In higher vertebrates, sulfatases belong to a conserved family of enzymes that are involved in the regulation of cell metabolism
and in developmental cell signaling. They cleave the sulfate from sulfate esters contained in hormones, proteins, and complex
macromolecules. A highly conserved cysteine in their active site is post-translationally converted into formylglycine by the
formylglycine-generating enzyme encoded by SUMF1 (sulfatase modifying factor 1). This post-translational modification activates all sulfatases. Sulfatases are extensively
glycosylated proteins and some of them follow trafficking pathways through cells, being secreted and taken up by distant cells.
Many proteoglycans, glycoproteins, and glycolipids contain sulfated carbohydrates, which are sulfatase substrates. Indeed,
sulfatases operate as decoding factors for a large amount of biological information contained in the structures of the sulfated
sugar chains that are covalently linked to proteins and lipids. Modifications to these sulfate groups have pivotal roles in
modulating specific signaling pathways and cell metabolism in mammals. 相似文献
17.
The CLE family of plant polypeptide signaling molecules 总被引:4,自引:0,他引:4
Polypeptide ligands have long been recognized as primary signaling molecules in diverse physiological processes in animal systems. Recent studies in plants have provided major breakthroughs with the discovery that small polypeptides are also involved in many plant biological processes, indicating that the use of polypeptides as signaling molecules in cell-to-cell communication is evolutionarily conserved. The CLAVATA3 (CLV3)/ENDOSPERM SURROUNDING REGION (ESR)-related (CLE) proteins are currently the best understood family of small polypeptides in plants. The recent isolation of MCLV3 from Arabidopsis and TDIF from a Zinnia cell culture system indicates that biologically active CLE polypeptides are produced by post-translational proteolysis and modification, similar to peptide hormone production in animals and yeast. Here, we review exciting discoveries involving the identification of the CLE proteins and their functions in various aspects of plant development, including restriction of stem cell accumulation by CLV3 and inhibition of xylem differentiation by TDIF. 相似文献
18.
Reichert N Choukrallah MA Matthias P 《Cellular and molecular life sciences : CMLS》2012,69(13):2173-2187
Class I Histone deacetylases (HDACs) play a central role in controlling cell cycle regulation, cell differentiation, and tissue development. These enzymes exert their function by deacetylating histones and a growing number of non-histone proteins, thereby regulating gene expression and several other cellular processes. Class I HDACs comprise four members: HDAC1, 2, 3, and 8. Deletion and/or overexpression of these enzymes in mammalian systems has provided important insights about their functions and mechanisms of action which are reviewed here. In particular, unique as well as redundant functions have been identified in several paradigms. Studies with small molecule inhibitors of HDACs have demonstrated the medical relevance of these enzymes and their potential as therapeutic targets in cancer and other pathological conditions. Going forward, better understanding the specific role of individual HDACs in normal physiology as well as in pathological settings will be crucial to exploit this protein family as a useful therapeutic target in a range of diseases. Further dissection of the pathways they impinge on and of their targets, in chromatin or otherwise, will form important avenues of research for the future. 相似文献
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20.
Jung-Eun Park Nak-Kyun Soung Yoshikazu Johmura Young H. Kang Chenzhong Liao Kyung H. Lee Chi Hoon Park Marc C. Nicklaus Kyung S. Lee 《Cellular and molecular life sciences : CMLS》2010,67(12):1957-1970
Members of the polo subfamily of protein kinases have emerged as important regulators in diverse aspects of the cell cycle
and cell proliferation. A large body of evidence suggests that a highly conserved polo-box domain (PBD) present in the C-terminal
non-catalytic region of polo kinases plays a pivotal role in the function of these enzymes. Recent advances in our comprehension
of the mechanisms underlying mammalian polo-like kinase 1 (Plk1)-dependent protein–protein interactions revealed that the
PBD serves as an essential molecular mediator that brings the kinase domain of Plk1 into proximity with its substrates, mainly
through phospho-dependent interactions with its target proteins. In this review, current understanding of the structure and
functions of PBD, mode of PBD-dependent interactions and substrate phosphorylation, and other phospho-independent functions
of PBD are discussed. 相似文献