排序方式: 共有50条查询结果,搜索用时 46 毫秒
21.
Cara L Ryan David C Baranowski Babykumari P Chitramuthu Suneil Malik Zhi Li Mingju Cao Sandra Minotti Heather D Durham Denis G Kay Christopher A Shaw Hugh PJ Bennett Andrew Bateman 《BMC neuroscience》2009,10(1):1-22
Background
Progranulin is a secreted high molecular weight growth factor bearing seven and one half copies of the cysteine-rich granulin-epithelin motif. While inappropriate over-expression of the progranulin gene has been associated with many cancers, haploinsufficiency leads to atrophy of the frontotemporal lobes and development of a form of dementia (frontotemporal lobar degeneration with ubiquitin positive inclusions, FTLD-U) associated with the formation of ubiquitinated inclusions. Recent reports indicate that progranulin has neurotrophic effects, which, if confirmed would make progranulin the only neuroprotective growth factor that has been associated genetically with a neurological disease in humans. Preliminary studies indicated high progranulin gene expression in spinal cord motor neurons. However, it is uncertain what the role of Progranulin is in normal or diseased motor neuron function. We have investigated progranulin gene expression and subcellular localization in cultured mouse embryonic motor neurons and examined the effect of progranulin over-expression and knockdown in the NSC-34 immortalized motor neuron cell line upon proliferation and survival.Results
In situ hybridisation and immunohistochemical techniques revealed that the progranulin gene is highly expressed by motor neurons within the mouse spinal cord and in primary cultures of dissociated mouse embryonic spinal cord-dorsal root ganglia. Confocal microscopy coupled to immunocytochemistry together with the use of a progranulin-green fluorescent protein fusion construct revealed progranulin to be located within compartments of the secretory pathway including the Golgi apparatus. Stable transfection of the human progranulin gene into the NSC-34 motor neuron cell line stimulates the appearance of dendritic structures and provides sufficient trophic stimulus to survive serum deprivation for long periods (up to two months). This is mediated at least in part through an anti-apoptotic mechanism. Control cells, while expressing basal levels of progranulin do not survive in serum free conditions. Knockdown of progranulin expression using shRNA technology further reduced cell survival.Conclusion
Neurons are among the most long-lived cells in the body and are subject to low levels of toxic challenges throughout life. We have demonstrated that progranulin is abundantly expressed in motor neurons and is cytoprotective over prolonged periods when over-expressed in a neuronal cell line. This work highlights the importance of progranulin as neuroprotective growth factor and may represent a therapeutic target for neurodegenerative diseases including motor neuron disease. 相似文献22.
23.
24.
25.
26.
27.
28.
29.
30.
27Al double rotation (DOR) NMR spectroscopy has been applied to investigate the framework ordering in the aluminophosphate molecular sieve AlPO4-8 during the hydration process. Relative well-resolved peaks in the DOR spectra of both dehydrated and successively rehydrated AlPO4-8 allow the isotropic shifts and the quadrupolar shifts to be correlated with the local framework structure. The rather complex interaction of water with AlPO4-8 occurs in a specific way, not randomly. For dehydrated AlPO4-8 efforts are shown to correlate respectively the isotropic shifts to the mean Al-O-P angles and the quadrupolar coupling constants to the shear strains of the different aluminium sites. 相似文献