排序方式: 共有71条查询结果,搜索用时 132 毫秒
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Federica Rizzo Giulietta Riboldi Sabrina Salani Monica Nizzardo Chiara Simone Stefania Corti Eva Hedlund 《Cellular and molecular life sciences : CMLS》2014,71(6):999-1015
Neurodegenerative disorders are characterized by the selective vulnerability and progressive loss of discrete neuronal populations. Non-neuronal cells appear to significantly contribute to neuronal loss in diseases such as amyotrophic lateral sclerosis (ALS), Parkinson, and Alzheimer’s disease. In ALS, there is deterioration of motor neurons in the cortex, brainstem, and spinal cord, which control voluntary muscle groups. This results in muscle wasting, paralysis, and death. Neuroinflammation, characterized by the appearance of reactive astrocytes and microglia as well as macrophage and T-lymphocyte infiltration, appears to be highly involved in the disease pathogenesis, highlighting the involvement of non-neuronal cells in neurodegeneration. There appears to be cross-talk between motor neurons, astrocytes, and immune cells, including microglia and T-lymphocytes, which are subsequently activated. Currently, effective therapies for ALS are lacking; however, the non-cell autonomous nature of ALS may indicate potential therapeutic targets. Here, we review the mechanisms of action of astrocytes, microglia, and T-lymphocytes in the nervous system in health and during the pathogenesis of ALS. We also evaluate the therapeutic potential of these cellular populations, after transplantation into ALS patients and animal models of the disease, in modulating the environment surrounding motor neurons from pro-inflammatory to neuroprotective. We also thoroughly discuss the recent advances made in the field and caveats that need to be overcome for clinical translation of cell therapies aimed at modulating non-cell autonomous events to preserve remaining motor neurons in patients. 相似文献
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GIBSON Ian SAVALANI Monica M LAM Christopher X F OLKOWSKI Radoslow EKAPUTRA Andrew K TAN Kim Cheng HUTMACHER Dietmar W 《清华大学学报》2009,(Z1):13-19
This paper describes fabrication of scaffolds for load-bearing applications, with primary consideration from the manufacturing perspective. An extrusion device, inspired by the FDM process, was used to create scaffolds from a variety of different polymeric materials and mixtures. The effectiveness of these scaffolds to host cells for bone regeneration has been investigated. This ongoing work has generated significant insight into the future direction of research and the possibilities of developing scaffolds for medium/high load-bearing applications. 相似文献
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Lu X Le Noble F Yuan L Jiang Q De Lafarge B Sugiyama D Bréant C Claes F De Smet F Thomas JL Autiero M Carmeliet P Tessier-Lavigne M Eichmann A 《Nature》2004,432(7014):179-186
Blood vessels and nerves are complex, branched structures that share a high degree of anatomical similarity. Guidance of vessels and nerves has to be exquisitely regulated to ensure proper wiring of both systems. Several regulators of axon guidance have been identified and some of these are also expressed in endothelial cells; however, the extent to which their guidance functions are conserved in the vascular system is still incompletely understood. We show here that the repulsive netrin receptor UNC5B is expressed by endothelial tip cells of the vascular system. Disruption of the Unc5b gene in mice, or of Unc5b or netrin-1a in zebrafish, leads to aberrant extension of endothelial tip cell filopodia, excessive vessel branching and abnormal navigation. Netrin-1 causes endothelial filopodial retraction, but only when UNC5B is present. Thus, UNC5B functions as a repulsive netrin receptor in endothelial cells controlling morphogenesis of the vascular system. 相似文献
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Caerulein, infused in normal subjects, significantly reduces serum Calcium levels; in addition, when infused 60 or 90 min after radioactive calcium, it increases the specific plasma radioactivity, in a manner similar to calcitonin. These results suggest that in man caerulein stimulates calcitonin release. 相似文献
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Kile BT Hentges KE Clark AT Nakamura H Salinger AP Liu B Box N Stockton DW Johnson RL Behringer RR Bradley A Justice MJ 《Nature》2003,425(6953):81-86
Now that the mouse and human genome sequences are complete, biologists need systematic approaches to determine the function of each gene. A powerful way to discover gene function is to determine the consequence of mutations in living organisms. Large-scale production of mouse mutations with the point mutagen N-ethyl-N-nitrosourea (ENU) is a key strategy for analysing the human genome because mouse mutants will reveal functions unique to mammals, and many may model human diseases. To examine genes conserved between human and mouse, we performed a recessive ENU mutagenesis screen that uses a balancer chromosome, inversion chromosome 11 (refs 4, 5). Initially identified in the fruitfly, balancer chromosomes are valuable genetic tools that allow the easy isolation of mutations on selected chromosomes. Here we show the isolation of 230 new recessive mouse mutations, 88 of which are on chromosome 11. This genetic strategy efficiently generates and maps mutations on a single chromosome, even as mutations throughout the genome are discovered. The mutations reveal new defects in haematopoiesis, craniofacial and cardiovascular development, and fertility. 相似文献
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Inherent toxicity of aggregates implies a common mechanism for protein misfolding diseases 总被引:68,自引:0,他引:68
Bucciantini M Giannoni E Chiti F Baroni F Formigli L Zurdo J Taddei N Ramponi G Dobson CM Stefani M 《Nature》2002,416(6880):507-511
A range of human degenerative conditions, including Alzheimer's disease, light-chain amyloidosis and the spongiform encephalopathies, is associated with the deposition in tissue of proteinaceous aggregates known as amyloid fibrils or plaques. It has been shown previously that fibrillar aggregates that are closely similar to those associated with clinical amyloidoses can be formed in vitro from proteins not connected with these diseases, including the SH3 domain from bovine phosphatidyl-inositol-3'-kinase and the amino-terminal domain of the Escherichia coli HypF protein. Here we show that species formed early in the aggregation of these non-disease-associated proteins can be inherently highly cytotoxic. This finding provides added evidence that avoidance of protein aggregation is crucial for the preservation of biological function and suggests common features in the origins of this family of protein deposition diseases. 相似文献