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1.
Chiara Mencarelli Pilar Martinez–Martinez 《Cellular and molecular life sciences : CMLS》2013,70(2):181-203
Ceramide, the precursor of all complex sphingolipids, is a potent signaling molecule that mediates key events of cellular pathophysiology. In the nervous system, the sphingolipid metabolism has an important impact. Neurons are polarized cells and their normal functions, such as neuronal connectivity and synaptic transmission, rely on selective trafficking of molecules across plasma membrane. Sphingolipids are abundant on neural cellular membranes and represent potent regulators of brain homeostasis. Ceramide intracellular levels are fine-tuned and alteration of the sphingolipid–ceramide profile contributes to the development of age-related, neurological and neuroinflammatory diseases. The purpose of this review is to guide the reader towards a better understanding of the sphingolipid–ceramide pathway system. First, ceramide biology is presented including structure, physical properties and metabolism. Second, we describe the function of ceramide as a lipid second messenger in cell physiology. Finally, we highlight the relevance of sphingolipids and ceramide in the progression of different neurodegenerative diseases. 相似文献
2.
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
3.
Fernando de Castro Ana Bribián Mª Cristina Ortega 《Cellular and molecular life sciences : CMLS》2013,70(22):4355-4368
Oligodendrocytes are the myelin-forming cells in the central nervous system (CNS). These cells originate from oligodendrocyte precursor cells (OPCs) during development, and they migrate extensively from oligodendrogliogenic niches along the neural tube to colonise the entire CNS. Like many other such events, this migratory process is precisely regulated by a battery of positional and signalling cues that act via their corresponding receptors and that are expressed dynamically by OPCs. Here, we will review the cellular and molecular basis of this important event during embryonic and postnatal development, and we will discuss the relevance of the substantial number of OPCs existing in the adult CNS. Similarly, we will consider the behaviour of OPCs in normal and pathological conditions, especially in animal models of demyelination and of the demyelinating disease, multiple sclerosis. The spontaneous remyelination observed after damage in demyelinating pathologies has a limited effect. Understanding the cellular and molecular mechanisms underlying the biology of OPCs, particularly adult OPCs, should help in the design of neuroregenerative strategies to combat multiple sclerosis and other demyelinating diseases. 相似文献
4.
5.
Prion protein, a misfolded isoform of which is the essential component of the agent of prion diseases, still remains an enigmatic
protein whose physiological functions are at best hypothetical. To gain a better insight into its putative role, many studies
were undertaken to look for molecules that bind prion protein, and have notably identified divalent metal ions, several proteins,
and nucleic acids. At first sight, the diversity of prion protein’s ligands seems of little help to infer a plausible function.
However, the intrinsically disordered property of its N-terminal tail and the potential of the protein to adopt a transmembrane
topology, can both be taken into account to predict its different states during its cellular cycle and its possible functions,
of which the most promising correspond to a general scavenger, a sensor or adaptor in a signaling cascade, and an RNA chaperone.
Received 16 August 2006; received after revision 7 November 2006; accepted 13 December 2006 相似文献
6.
Primary cilia are a class of cilia that are typically solitary, immotile appendages present on nearly every mammalian cell
type. Primary cilia are believed to perform specialized sensory and signaling functions that are important for normal development
and cellular homeostasis. Indeed, primary cilia dysfunction is now linked to numerous human diseases and genetic disorders.
Collectively, primary cilia disorders are termed as ciliopathies and present with a wide range of clinical features, including
cystic kidney disease, retinal degeneration, obesity, polydactyly, anosmia, intellectual disability, and brain malformations.
Although significant progress has been made in elucidating the functions of primary cilia on some cell types, the precise
functions of most primary cilia remain unknown. This is particularly true for primary cilia on neurons throughout the mammalian
brain. This review will introduce primary cilia and ciliary signaling pathways with a focus on neuronal cilia and their putative
functions and roles in human diseases. 相似文献
7.
Several serine proteases including thrombin, tissue-type plasminogen activator and urokinase-type plasminogen activator have
been well characterized in the brain. In this article, we review the brain-related trypsin and trypsin-like serine proteases.
Accumulating evidence demonstrates that trypsin and trypsin-like serine proteases play very important roles in neural development,
plasticity, neurodegeneration and neuroregeneration in the brain. Neuropsin is able to hydrolyze the extracellular matrix
components by its active site serine, and regulates learning and memory in normal brain. The mutant neurotrypsin contributes
to mental retardation in children. Neurosin seems to be involved in the pathogenesis of neurodegenerative disorders, like
Alzheimer’s disease, Parkinson’s disease or multiple sclerosis. Although mesotrypsin/trypsin IV is also implicated in neurodegeneration,
its functional significance still remains largely unknown. Particularly, mesotrypsin/trypsin IV, P22 and neurosin exert their
physiological and pathological functions through activation of certain protease-activated receptors (PARs). In the brain,
the presence of serpins controls the activity of serine proteases. Therefore, understanding the interaction among brain trypsin,
serpins and PARs will provide invaluable tools for regulating normal brain functions and for the clinical treatment of neural
disorders.
Y. Wang, W. Luo: These authors made equal contributions.
Received 26 June 2007; received after revision 13 August 2007; accepted 12 September 2007 相似文献
8.
José L. Barbero 《Cellular and molecular life sciences : CMLS》2009,66(13):2025-2035
Cells have evolved to develop molecules and control mechanisms that guarantee correct chromosome segregation and ensure the
proper distribution of genetic material to daughter cells. In this sense, the establishment, maintenance, and removal of sister
chromatid cohesion is one of the most fascinating and dangerous processes in the life of a cell because errors in the control
of these processes frequently lead to cell death or aneuploidy. The main protagonist in this mechanism is a four-protein complex
denominated the cohesin complex. In the last 10 years, we have improved our understanding of the key players in the regulation
of sister chromatid cohesion during cell division in mitosis and meiosis. The last 2 years have seen an increase in evidence
showing that cohesins have important functions in non-dividing cells, revealing new, unexplored roles for these proteins in
the control of gene expression, development, and other essential cell functions in mammals. 相似文献
9.
Christiana Ruhrberg Victoria L. Bautch 《Cellular and molecular life sciences : CMLS》2013,70(10):1675-1684
The developing central nervous system (CNS) is vascularized via ingression of blood vessels from the outside as the neural tissue expands. This angiogenic process occurs without perturbing CNS architecture due to exquisite cross-talk between the neural compartment and invading blood vessels. Subsequently, this intimate relationship also promotes the formation of the neurovascular unit that underlies the blood–brain barrier and regulates blood flow to match brain activity. This review provides a historical perspective on research into CNS blood vessel growth and patterning, discusses current models used to study CNS angiogenesis, and provides an overview of the cellular and molecular mechanisms that promote blood vessel growth and maturation. Finally, we highlight the significance of these mechanisms for two different types of neurovascular CNS disease. 相似文献
10.
Neural stem cells (NSCs) in the adult mammalian brain proliferate and continuously produce new neurons. To date, there has
been little research into the functions of lectins in adult NSCs. Recently, we reported that a lectin, galectin-1, is expressed
on adult NSCs and promotes their proliferation through its carbohydrate-binding ability. This evidence raises the possibility
that glycans play roles in the proliferation of adult NSCs.
Received 6 November 2006; received after revision 13 December 2006; accepted 15 February 2007 相似文献
11.
The search for migraine genes: an overview of current knowledge 总被引:3,自引:0,他引:3
Colson NJ Fernandez F Lea RA Griffiths LR 《Cellular and molecular life sciences : CMLS》2007,64(3):331-344
Migraine is a complex familial condition that imparts a significant burden on society. There is evidence for a role of genetic
factors in migraine, and elucidating the genetic basis of this disabling condition remains the focus of much research. In
this review we discuss results of genetic studies to date, from the discovery of the role of neural ion channel gene mutations
in familial hemiplegic migraine (FHM) to linkage analyses and candidate gene studies in the more common forms of migraine.
The success of FHM regarding discovery of genetic defects associated with the disorder remains elusive in common migraine,
and causative genes have not yet been identified. Thus we suggest additional approaches for analysing the genetic basis of
this disorder. The continuing search for migraine genes may aid in a greater understanding of the mechanisms that underlie
the disorder and potentially lead to significant diagnostic and therapeutic applications.
Received 16 December 2005; received after revision 9 October 2006; accepted 13 November 2006 相似文献
12.
Wanjun Zhu Xiao-Yan Zhang Sadie L. Marjani Jialing Zhang Wengeng Zhang Shixiu Wu Xinghua Pan 《Cellular and molecular life sciences : CMLS》2017,74(5):869-880
Single-cell sequencing (SCS) is a fast-growing, exciting field in genomic medicine. It enables the high-resolution study of cellular heterogeneity, and reveals the molecular basis of complicated systems, which facilitates the identification of new biomarkers for diagnosis and for targeting therapies. It also directly promotes the next generation of genomic medicine because of its ultra-high resolution and sensitivity that allows for the non-invasive and early detection of abnormalities, such as aneuploidy, chromosomal translocation, and single-gene disorders. This review provides an overview of the current progress and prospects for the diagnostic applications of SCS, specifically in pre-implantation genetic diagnosis/screening, non-invasive prenatal diagnosis, and analysis of circulating tumor cells. These analyses will accelerate the early and precise control of germline- or somatic-mutation-based diseases, particularly single-gene disorders, chromosome abnormalities, and cancers. 相似文献
13.
The central nervous system (CNS) is considered an immune-privileged organ that maintains an adaptable immune surveillance
system. Dysregulated immune function within the CNS contributes to the development of brain tumor growth, and robust immune
activation results in excessive inflammation. Human lymphocyte antigen-G (HLA-G) proteins with tolerogenic immunoreactivity
have been implicated in various pathophysiological processes including immune surveillance, governing homeostasis and immune
regulation. In this review, we describe the wealth of evidence for the involvement of HLA-G in the CNS under physiological
and pathological conditions. Further, we review regulatory functions that may be applicable as beneficial strategies in the
therapeutic manipulation of immune-mediated CNS immune responses. Additionally, we try to understand how this molecule cooperates
with other CNS-resident cells to maintain normal immune homeostasis, while still facilitating the development of the appropriate
immune responses. 相似文献
14.
Mario Vallon Junlei Chang Haijing Zhang Calvin J. Kuo 《Cellular and molecular life sciences : CMLS》2014,71(18):3489-3506
Angiogenesis, the formation of new blood vessels from pre-existing vessels, in the central nervous system (CNS) is seen both as a normal physiological response as well as a pathological step in disease progression. Formation of the blood–brain barrier (BBB) is an essential step in physiological CNS angiogenesis. The BBB is regulated by a neurovascular unit (NVU) consisting of endothelial and perivascular cells as well as vascular astrocytes. The NVU plays a critical role in preventing entry of neurotoxic substances and regulation of blood flow in the CNS. In recent years, research on numerous acquired and hereditary disorders of the CNS has increasingly emphasized the role of angiogenesis in disease pathophysiology. Here, we discuss molecular mechanisms of CNS angiogenesis during embryogenesis as well as various pathological states including brain tumor formation, ischemic stroke, arteriovenous malformations, and neurodegenerative diseases. 相似文献
15.
The hypothesis of the preferred X-chromosome loss in elder human females was reevaluated in the golden hamster: early castration of females proved that the increase of aneuploid cells is correlated with the loss of the ovaries. But here, and in old females, aneuploidy consisted of random loss of excess of chromosomes, in no case an X-chromosome. 相似文献
16.
Summary The hypothesis of the preferred X-chromosome loss in elder human females was reevaluated in the golden hamster: early castration of females proved that the increase of aneuploid cells is correlated with the loss of the ovaries. But here, and in old females, aneuploidy consisted of random loss or excess of chromosomes, in no case an X-chromosome. 相似文献
17.
Ina M. Wittko-Schneider Fabian T. Schneider Karl H. Plate 《Cellular and molecular life sciences : CMLS》2013,70(10):1705-1725
Vascular endothelial growth factors (VEGFs), initially thought to act specifically on the vascular system, exert trophic effects on neural cells during development and adulthood. Therefore, the VEGF system serves as a promising therapeutic target for brain pathologies, but its simultaneous action on vascular cells paves the way for harmful side effects. To circumvent these deleterious effects, many studies have aimed to clarify whether VEGFs directly affect neural cells or if the effects are mediated secondarily via other cell types, like vascular cells. A great number of reports have shown the expression and function of VEGF receptors (VEGFRs), mainly VEGFR-1 and -2, in neural cells, where VEGFR-2 has been described as the major mediator of VEGF-A signals. This review aims to summarize and compare the divergent roles of VEGFR-1 and -2 during CNS development and homeostasis. 相似文献
18.
Malaguarnera L 《Cellular and molecular life sciences : CMLS》2006,63(24):3018-3029
The enzyme chitotriosidase (ChT), the human analogue of chitinases from non-vertebrate species, is one of the most abundant
and indicative proteins secreted by activated macrophages. Its enzymatic activity is elevated in serum of patients suffering
from Gaucher’s disease type 1 and in some other inherited lysosomal storage disorders, as well as in diseases in which macrophages
are activated. The last decade has witnessed the appearance of a substantial number of studies attempting to unravel its cellular
functions, which have yet not been fully defined. A great deal of progress has been made in the study of the physiological
roles of ChT. This review is looks at the key areas of investigations addressed to further illuminate whether ChT activation
might have different functional meanings in various diseases.
Received 7 June 2006; received after revision 24 July 2006; accepted 21 September 2006 相似文献
19.
Do-Yeon Kim Inmoo Rhee Jihye Paik 《Cellular and molecular life sciences : CMLS》2014,71(21):4221-4241
Metabolic activity indicative of cellular demand is emerging as a key player in cell fate decision. Numerous studies have demonstrated that diverse metabolic pathways have a critical role in the control of the proliferation, differentiation and quiescence of stem cells. The identification of neural stem/progenitor cells (NSPCs) and the characterization of their development and fate decision process have provided insight into the regenerative potential of the adult brain. As a result, the potential of NSPCs in cell replacement therapies for neurological diseases is rapidly growing. The aim of this review is to discuss the recent findings on the crosstalk among key regulators of NSPC development and the metabolic regulation crucial for the function and cell fate decisions of NSPCs. Fundamental understanding of the metabolic circuits in NSPCs may help to provide novel approaches for reactivating neurogenesis to treat degenerative brain conditions and cognitive decline. 相似文献
20.
Gemoll T Habermann JK Lahmann J Szymczak S Lundgren C Bündgen NK Jungbluth T Nordström B Becker S Lomnytska MI Bruch HP Ziegler A Hellman U Auer G Roblick UJ Jörnvall H 《Cellular and molecular life sciences : CMLS》2012,69(2):325-333
DNA aneuploidy has been identified as a prognostic factor in the majority of epithelial malignancies. We aimed at identifying ploidy-associated protein expression in endometrial cancer of different prognostic subgroups. Comparison of gel electrophoresis-based protein expression patterns between normal endometrium (n?=?5), diploid (n?=?7), and aneuploid (n?=?7) endometrial carcinoma detected 121 ploidy-associated protein forms, 42 differentially expressed between normal endometrium and diploid endometrioid carcinomas, 37 between diploid and aneuploid endometrioid carcinomas, and 41 between diploid endometrioid and aneuploid uterine papillary serous cancer. Proteins were identified by mass spectrometry and evaluated by Ingenuity Pathway Analysis. Targets were confirmed by liquid chromatography/mass spectrometry. Mass spectrometry identified 41 distinct polypeptides and pathway analysis resulted in high-ranked networks with vimentin and Nf-κB as central nodes. These results identify ploidy-associated protein expression differences that overrule histopathology-associated expression differences and emphasize particular protein networks in genomic stability of endometrial cancer. 相似文献