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11.
NJ Krautler V Kana J Kranich Y Tian D Perera D Lemm P Schwarz A Armulik JL Browning M Tallquist T Buch JB Oliveira-Martins C Zhu M Hermann U Wagner R Brink M Heikenwalder A Aguzzi 《Cell》2012,150(1):194-206
The differentiation of follicular dendritic cells (FDC) is essential to the remarkable microanatomic plasticity of lymphoid follicles. Here we show that FDC arise from ubiquitous perivascular precursors (preFDC) expressing platelet-derived growth factor receptor β (PDGFRβ). PDGFRβ-Cre-driven reporter gene recombination resulted in FDC labeling, whereas conditional ablation of PDGFRβ(+)-derived cells abolished FDC, indicating that FDC originate from PDGFRβ(+) cells. Lymphotoxin-α-overexpressing prion protein (PrP)(+) kidneys developed PrP(+) FDC after transplantation into PrP(-) mice, confirming that preFDC exist outside lymphoid organs. Adipose tissue-derived PDGFRβ(+) stromal-vascular cells responded to FDC maturation factors and, when transplanted into lymphotoxin β receptor (LTβR)(-) kidney capsules, differentiated into Mfge8(+)CD21/35(+)FcγRIIβ(+)PrP(+) FDC capable of trapping immune complexes and recruiting B cells. Spleens of lymphocyte-deficient mice contained perivascular PDGFRβ(+) FDC precursors whose expansion required both lymphoid tissue inducer (LTi) cells and lymphotoxin. The ubiquity of preFDC and their strategic location at blood vessels may explain the de novo generation of organized lymphoid tissue at sites of lymphocytic inflammation. 相似文献
12.
Aguzzi A 《Journal of neurochemistry》2006,97(6):1726-1739
Neuronal vacuolation (spongiosis), neuronal death, and pronounced glial reactions are the hallmarks of transmissible spongiform encephalopathies (TSEs), or prion diseases. A wealth of physical, biochemical, and immunological evidence indicates that the TSE agent, termed prion, does not contain agent-specific nucleic acid encoding its own constituents, as is the case for all other infectious pathogens. Also, no adaptive immune responses are elicited upon infection. A defining feature of TSEs is the deposition, mainly in the brain and lymphoreticular tissues, of an aggregated and structurally abnormal protein, designated PrP(Sc) or PrP-res, which represents a conformational isomer of the ubiquitous surface protein PrP(C). Biochemical and genetic evidence link PrP and its gene to the disease. Although TSEs are by definition transmissible, a growing number of Prnp-associated non-infectious neurodegenerative proteinopathies are now being recognized. 相似文献
13.
A wealth of evidence points to an abnormal form of the prion protein called PrP(Sc) as the transmissible agent responsible for prion diseases. However, the physiological function of its normal conformer, the cellular prion protein (PrP(C)), is still unknown. Recently, a homologue of PrP(C) was discovered and denoted Doppel (Dpl). In contrast to PrP, mice deficient for Dpl suffer from an important pathological phenotype: male sterility. This phenotype shifts the attention from the brain, where most of the investigations on Dpl have been performed, to testis, raising hope to resolve the long lasting search of PrP(C) function. 相似文献
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Transepithelial prion transport by M cells 总被引:11,自引:0,他引:11
Heppner FL Christ AD Klein MA Prinz M Fried M Kraehenbuhl JP Aguzzi A 《Nature medicine》2001,7(9):976-977
16.
Carbonaro M Grant G Mattera M Aguzzi A Pusztai A 《Biological trace element research》2001,84(1-3):181-196
Chemical composition and content in polyphenols, phytic acid, and dietary fiber of whole cooked common bean (Phaseolus vulgaris L.) and faba bean (Vicia faba L.) and of soluble and insoluble fractions separated from them were determined. Simultaneous determination of Cu, Fe, and
protein bioavailability in the small intestine of rat was carried out in single-dose, short-term (1 h) experiments. After
cooking, about 80% of seed components (on a weight basis) of either legume was recovered in the precipitate (insoluble fraction)
after extraction with water. Protein, lipid, starch, dietary fiber, and polyphenols underwent the most severe insolubilization,
together with more than 70% of total Cu and Fe. Cu, Fe, and protein bioavailability showed a similar trend (i.e., the lower
the protein, the lower the Cu and Fe availability). Availability of proteins, Cu, and Fe in the insoluble fractions were the
lowest, but Cu bioavailability was higher than that of Fe in all fractions. The results provide evidence that the heat-induced
insolubilization process adversely affects not only protein but also Cu and Fe bioavailability from legumes and that polyphenols
are likely to be a major inhibitor on absorption. 相似文献
17.
Prion diseases are characterized by the deposition of PrP(Sc), an abnormal form of the cellular prion protein PrP(C), which is encoded by the Prnp gene. PrP(C) is highly expressed on neurons and its function is unknown. Recombinant PrP(C) was claimed to possess superoxide dismutase (SOD) activity, and it was hypothesized that abrogation of this function may contribute to neurodegeneration in prion diseases. We tested this hypothesis in vivo by studying copper/zinc and manganese SOD activity in genetically defined crosses of mice lacking the Sod1 gene with mice lacking PrP(C), and with hemizygous or homozygous tga20 transgenic mice overexpressing various levels of PrP(C). We failed to detect any influence of the Prnp genotype and gene dosage on SOD1 or SOD2 activity in heart, spleen, brain, and synaptosome-enriched brain fractions. Control experiments included crosses of mice lacking or overexpressing PrPc with mice overexpressing human Cu2+/Zn2+-superoxide dismutase, and confirmed that SOD enzymatic activity correlated exclusively with the gene dosage of bona fide human or murine SOD. We conclude that PrP(C) in vivo does not discernibly contribute to total SOD activity and does not possess an intrinsic dismutase activity. 相似文献
18.
Expression of truncated PrP targeted to Purkinje cells of PrP knockout mice causes Purkinje cell death and ataxia 总被引:4,自引:0,他引:4
Flechsig E Hegyi I Leimeroth R Zuniga A Rossi D Cozzio A Schwarz P Rülicke T Götz J Aguzzi A Weissmann C 《The EMBO journal》2003,22(12):3095-3101
PrP knockout mice with disruption of only the PrP-encoding region (Zürich I-type) remain healthy, whereas mice with deletions extending upstream of the PrP-encoding exon (Nagasaki-type) suffer Purkinje cell loss and ataxia, associated with ectopic expression of Doppel in brain, particularly in Purkinje cells. The phenotype is abrogated by co-expression of full-length PrP. Doppel is 25% similar to PrP, has the same globular fold, but lacks the flexible N-terminal tail. We now show that in Zürich I-type PrP-null mice, expression of N-terminally truncated PrP targeted to Purkinje cells also leads to Purkinje cell loss and ataxia, which are reversed by PrP. Doppel and truncated PrP probably cause Purkinje cell degeneration by the same mechanism. 相似文献
19.
Pathogenesis of prion diseases: a progress report 总被引:3,自引:0,他引:3
Almost 20 years have passed since Stanley Prusiner proposed that the agent causing transmissible spongiform encephalopathies consists exclusively of a protein and termed it prion. A mixed balance can be drawn from the enormous research efforts that have gone into prion research during this time. On the negative side, the protein-only hypothesis has not been conclusively proven yet. On the positive side, our understanding of spongiform encephalopathies has experienced tremendous advances, mostly through human genetics, mouse transgenetics, and biophysical methods. Perhaps the most astonishing development is the realization that many human neurodegenerative diseases for which transmissibility has been more or less stringently excluded, may follow pathogenetic principles similar to those of prion diseases. Also, the hypothesis that prion-like phenomena may underlie certain non-genetic traits observed in yeast has resulted in the surprising recognition that the instructional self-propagating changes in protein conformation may be much more prevalent in nature than previously thought. The latter developments have been astonishingly successful, and one could now argue that the prion principle is much more solidly established in yeast than in mammals. 相似文献
20.