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61.
62.
Farooqui AA Farooqui T Panza F Frisardi V 《Cellular and molecular life sciences : CMLS》2012,69(5):741-762
The metabolic syndrome is a cluster of common pathologies: abdominal obesity linked to an excess of visceral fat, insulin
resistance, dyslipidemia and hypertension. At the molecular level, metabolic syndrome is accompanied not only by dysregulation
in the expression of adipokines (cytokines and chemokines), but also by alterations in levels of leptin, a peptide hormone
released by white adipose tissue. These changes modulate immune response and inflammation that lead to alterations in the
hypothalamic ‘bodyweight/appetite/satiety set point,’ resulting in the initiation and development of metabolic syndrome. Metabolic
syndrome is a risk factor for neurological disorders such as stroke, depression and Alzheimer’s disease. The molecular mechanism
underlying the mirror relationship between metabolic syndrome and neurological disorders is not fully understood. However,
it is becoming increasingly evident that all cellular and biochemical alterations observed in metabolic syndrome like impairment
of endothelial cell function, abnormality in essential fatty acid metabolism and alterations in lipid mediators along with
abnormal insulin/leptin signaling may represent a pathological bridge between metabolic syndrome and neurological disorders
such as stroke, Alzheimer’s disease and depression. The purpose of this review is not only to describe the involvement of
brain in the pathogenesis of metabolic syndrome, but also to link the pathogenesis of metabolic syndrome with neurochemical
changes in stroke, Alzheimer’s disease and depression to a wider audience of neuroscientists with the hope that this discussion
will initiate more studies on the relationship between metabolic syndrome and neurological disorders. 相似文献
63.
Sieni E Cetica V Mastrodicasa E Pende D Moretta L Griffiths G Aricò M 《Cellular and molecular life sciences : CMLS》2012,69(1):29-40
Cytotoxic T lymphocytes, natural killer cells, and NKT cells are effector cells able to kill infected cells. In some inherited
human disorders, a defect in selected proteins involved in the cellular cytotoxicity mechanism results in specific clinical
syndromes, grouped under the name of familial hemophagocytic lymphohistiocytosis. Recent advances in genetic studies of these
patients has allowed the identification of different genetic subsets. Additional genetic immune deficiencies may also induce
a similar clinical picture. International cooperation and prospective trials resulted in refining the diagnostic and therapeutic
approach to these rare diseases with improved outcome but also with improved knowledge of the mechanisms underlying granule-mediated
cellular cytotoxicity in humans. 相似文献
64.
Microautophagy: lesser-known self-eating 总被引:1,自引:1,他引:0
Microautophagy, the non-selective lysosomal degradative process, involves direct engulfment of cytoplasmic cargo at a boundary
membrane by autophagic tubes, which mediate both invagination and vesicle scission into the lumen. With its constitutive characteristics,
microautophagy of soluble substrates can be induced by nitrogen starvation or rapamycin via regulatory signaling complex pathways.
The maintenance of organellar size, membrane homeostasis, and cell survival under nitrogen restriction are the main functions
of microautophagy. In addition, microautophagy is coordinated with and complements macroautophagy, chaperone-mediated autophagy,
and other self-eating pathways. Three forms of selective microautophagy, including micropexophagy, piecemeal microautophagy
of the nucleus, and micromitophagy, share common ground with microautophagy to some degree. As the accumulation of experimental
data, the precise mechanisms that govern microautophagy are becoming more appreciated. Here, we review the microautophagic
molecular machinery, its physiological functions, and relevance to human diseases, especially in diseases involving multivesicular
bodies and multivesicular lysosomes. 相似文献
65.
Chronic granulomatous disease (CGD) is an uncommon congenital immunodeficiency seen approximately in 1 of 250,000 individuals.
It is caused by a profound defect in a burst of oxygen consumption that normally accompanies phagocytosis in all myeloid cells
(neutrophils, eosinophils, monocytes, and macrophages). This “respiratory burst” involves the catalytic conversion of molecular
oxygen to the oxygen free-radical superoxide, which in turn gives rise to hydrogen peroxide, hypochlorous acid, and hydroxyl
radicals. These oxygen derivatives play a critical role in the killing of pathogenic bacteria and fungi. As a result of the
failure to activate the respiratory burst in their phagocytes, the majority of CGD patients suffer from severe recurrent infections
and rather unexplained prolonged inflammatory reactions that may result in granulomatous lesions. Both may cause severe organ
dysfunction depending on the tissues involved. Preventive measures as well as rapid (invasive) diagnostic procedures are required
to successfully treat CGD. Hematopoietic stem cell transplantation may be a serious option in some of the patients. 相似文献
66.
Machnicka B Grochowalska R Bogusławska DM Sikorski AF Lecomte MC 《Cellular and molecular life sciences : CMLS》2012,69(2):191-201
This review focuses on the recent advances in functions of spectrins in non-erythroid cells. We discuss new data concerning
the commonly known role of the spectrin-based skeleton in control of membrane organization, stability and shape, and tethering
protein mosaics to the cellular motors and to all major filament systems. Particular effort has been undertaken to highlight
recent advances linking spectrin to cell signaling phenomena and its participation in signal transduction pathways in many
cell types. 相似文献
67.
Xue B Mizianty MJ Kurgan L Uversky VN 《Cellular and molecular life sciences : CMLS》2012,69(8):1211-1259
Many proteins and protein regions are disordered in their native, biologically active states. These proteins/regions are abundant
in different organisms and carry out important biological functions that complement the functional repertoire of ordered proteins.
Viruses, with their highly compact genomes, small proteomes, and high adaptability for fast change in their biological and
physical environment utilize many of the advantages of intrinsic disorder. In fact, viral proteins are generally rich in intrinsic
disorder, and intrinsically disordered regions are commonly used by viruses to invade the host organisms, to hijack various
host systems, and to help viruses in accommodation to their hostile habitats and to manage their economic usage of genetic
material. In this review, we focus on the structural peculiarities of HIV-1 proteins, on the abundance of intrinsic disorder
in viral proteins, and on the role of intrinsic disorder in their functions. 相似文献
68.
69.
Gauthier LR Granotier C Hoffschir F Etienne O Ayouaz A Desmaze C Mailliet P Biard DS Boussin FD 《Cellular and molecular life sciences : CMLS》2012,69(4):629-640
Functional telomeres are protected from non-homologous end-joining (NHEJ) and homologous recombination (HR) DNA repair pathways.
Replication is a critical period for telomeres because of the requirement for reconstitution of functional protected telomere
conformations, a process that involves DNA repair proteins. Using knockdown of DNA-PKcs and Rad51 expression in three different
cell lines, we demonstrate the respective involvement of NHEJ and HR in the formation of telomere aberrations induced by the
G-quadruplex ligand 360A during or after replication. HR contributed to specific chromatid-type aberrations (telomere losses
and doublets) affecting the lagging strand telomeres, whereas DNA-PKcs-dependent NHEJ was responsible for sister telomere
fusions as a direct consequence of G-quadruplex formation and/or stabilization induced by 360A on parental telomere G strands.
NHEJ and HR activation at telomeres altered mitotic progression in treated cells. In particular, NHEJ-mediated sister telomere
fusions were associated with altered metaphase-anaphase transition and anaphase bridges and resulted in cell death during
mitosis or early G1. Collectively, these data elucidate specific molecular and cellular mechanisms triggered by telomere targeting
by the G-quadruplex ligand 360A, leading to cancer cell death. 相似文献
70.
Voltage-gated calcium channels are important mediators of calcium influx into electrically excitable cells. The amount of
calcium entering through this family of channel proteins is not only determined by the functional properties of channels embedded
in the plasma membrane but also by the numbers of channels that are expressed at the cell surface. The trafficking of channels
is controlled by numerous processes, including co-assembly with ancillary calcium channel subunits, ubiquitin ligases, and
interactions with other membrane proteins such as G protein coupled receptors. Here we provide an overview about the current
state of knowledge of calcium channel trafficking to the cell membrane, and of the mechanisms regulating the stability and
internalization of this important ion channel family. 相似文献