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The Alzheimer's disease (AD)-associated amyloid-β protein precursor (AβPP) is cleaved by α-, β-, and presenilin (PS)/γ-secretases through sequential regulated proteolysis. These proteolytic events control the generation of the pathogenic amyloid-β (Aβ) peptide, which excessively accumulates in the brains of individuals afflicted by AD. A growing number of additional proteins cleaved by PS/γ-secretase continue to be discovered. Similarly to AβPP, most of these proteins are type-I transmembrane proteins involved in vital signaling functions regulating cell fate, adhesion, migration, neurite outgrowth, or synaptogenesis. All the identified proteins share common structural features, which are typical for their proteolysis. The consequences of the PS/γ-secretase-mediated cleavage on the function of many of these proteins are largely unknown. Here, we review the current literature on the proteolytic processing mediated by the versatile PS/γ-secretase complex. We begin by discussing the steps of AβPP processing and PS/γ-secretase complex composition and localization, which give clues to how and where the processing of other PS/γ-secretase substrates may take place. Then we summarize the typical features of PS/γ-secretase-mediated protein processing. Finally, we recapitulate the current knowledge on the possible physiological function of PS/γ-secretase-mediated cleavage of specific substrate proteins. 相似文献
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Than NG Abdul Rahman O Magenheim R Nagy B Fule T Hargitai B Sammar M Hupuczi P Tarca AL Szabo G Kovalszky I Meiri H Sziller I Rigo J Romero R Papp Z 《Virchows Archiv : an international journal of pathology》2008,453(4):387-400
Placental protein 13 (PP13) is a galectin expressed by the syncytiotrophoblast. Women who subsequently develop preterm pre-eclampsia
have low first trimester maternal serum PP13 concentrations. This study revealed that third trimester maternal serum PP13
concentration increased with gestational age in normal pregnancies (p < 0.0001), and it was significantly higher in women presenting with preterm pre-eclampsia (p = 0.02) and hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome (p = 0.01) than in preterm controls. Conversely, placental PP13 mRNA (p = 0.03) and protein, as well as cytoplasmic PP13 staining of the syncytiotrophoblast (p < 0.05) was decreased in these pathological pregnancies compared to controls. No differences in placental expression and
serum concentrations of PP13 were found at term between patients with pre-eclampsia and control women. In contrast, the immunoreactivity
of the syncytiotrophoblast microvillous membrane was stronger in both term and preterm pre-eclampsia and HELLP syndrome than
in controls. Moreover, large syncytial cytoplasm protrusions, membrane blebs and shed microparticles strongly stained for
PP13 in pre-eclampsia and HELLP syndrome. In conclusion, parallel to its decreased placental expression, an augmented membrane
shedding of PP13 contributes to the increased third trimester maternal serum PP13 concentrations in women with preterm pre-eclampsia
and HELLP syndrome. 相似文献
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P. P. Garcia-Luna M.D. A. Leal-Cerro M.D. C. Montero M.D. B. W. Scheithauer M.D. A. Campanario M.D. C. Dieguez M.D. R. Astorga M.D. K. Kovacs M.D. Ph.D. 《Surgical neurology》1987,27(6):563-568
Ectopic production of growth hormone-releasing factor (GRF) is a rare cause of acromegaly. In addition to its production by gangliocytomas, both hypothalamic and intrasellar, in rare cases various neuroendocrine neoplasms produce the substance, with resultant growth hormone cell hyperplasia of the pituitary and acromegaly. We report an endocrinologically well-documented case of a GRF-producing bronchial carcinoid tumor in which the associated acromegaly was cured by lobectomy. 相似文献
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Chengqun Huang Smadar Yitzhaki Cynthia N. Perry Wayne Liu Zoltan Giricz Robert M. MentzerJr. Roberta A. Gottlieb 《Journal of cardiovascular translational research》2010,3(4):365-373
Based on growing evidence linking autophagy to preconditioning, we tested the hypothesis that autophagy is necessary for cardioprotection
conferred by ischemic preconditioning (IPC). We induced IPC with three cycles of 5 min regional ischemia alternating with
5 min reperfusion and assessed the induction of autophagy in mCherry-LC3 transgenic mice by imaging of fluorescent autophagosomes
in cryosections. We found a rapid and significant increase in the number of autophagosomes in the risk zone of the preconditioned
hearts. In Langendorff-perfused hearts subjected to an IPC protocol of 3 × 5 min ischemia, we also observed an increase in
autophagy within 10 min, as assessed by Western blotting for p62 and cadaverine dye binding. To establish the role of autophagy
in IPC cardioprotection, we inhibited autophagy with Tat-ATG5K130R, a dominant negative mutation of the autophagy protein Atg5. Cardioprotection by IPC was reduced in rat hearts perfused with
recombinant Tat-ATG5K130R. To extend the potential significance of autophagy in cardioprotection, we also assessed three structurally unrelated cardioprotective
agents—UTP, diazoxide, and ranolazine—for their ability to induce autophagy in HL-1 cells. We found that all three agents
induced autophagy; inhibition of autophagy abolished their protective effect. Taken together, these findings establish autophagy
as an end-effector in ischemic and pharmacologic preconditioning. 相似文献
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Chris Roelfsema Eva Kovacs Pauline Roos Dilva Terzano Mitchell Lyons Stuart Phinn 《Remote sensing letters.》2018,9(4):324-333
Coral reef scientists and managers require detailed information of reef environments to develop, implement and evaluate management strategies. Maps showing the distribution of corals, seagrass, algae, sand, rubble and rock are an essential component of this information. Using a semi-automated, object-based image analysis (OBIA) approach this study created a benthic community map for Heron Reef (area: approximately 27 km2), Southern Great Barrier Reef, Australia. Benthic cover information was acquired for calibration and validation via georeferenced photograph transects, which coincided with high spatial resolution Quickbird-2 satellite image capture in 2007. Through combination of these data sets and modification of a semi-automated OBIA classification scheme previously developed for seagrass environments to account for the heterogeneous nature of reef benthic communities, a benthic community map was created for Heron Reef with an overall accuracy of 61.6%. The robustness and repeatability of our method provide future opportunity to apply the semi-automated approach to a time series of field and high spatial resolution image data sets to create a time series of benthic community maps for Heron Reef. The results presented in this study therefore open up the opportunity to assess and understand the spatial and temporal dynamics of the reef environment. 相似文献