| 1. |
- Simard, Alain R, et al.
(författare)
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Bone marrow-derived microglia play a critical role in restricting senile plaque formation in Alzheimer's disease
- 2006
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Ingår i: Neuron. - : Elsevier BV. - 0896-6273. ; 49:4, s. 489-502
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Tidskriftsartikel (refereegranskat)abstract
- Microglia are the immune cells of the brain. Here we show a massive infiltration of highly ramified and elongated microglia within the core of amyloid plaques in transgenic mouse models of Alzheimer's disease (AD). Many of these cells originate from the bone marrow, and the beta-amyloid-40 and -42 isoforms are able to trigger this chemoattraction. These newly recruited cells also exhibit a specific immune reaction to both exogenous and endogenous beta-amyloid in the brain. Creation of a new AD transgenic mouse that expresses the thymidine kinase protein under the control of the CD11b promoter allowed us to show that blood-derived microglia and not their resident counterparts have the ability to eliminate amyloid deposits by a cell-specific phagocytic mechanism. These bone marrow-derived microglia are thus very efficient in restricting amyloid deposits. Therapeutic strategies aiming to improve their recruitment could potentially lead to a new powerful tool for the elimination of toxic senile plaques.
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| 2. |
- Soulet, Denis, et al.
(författare)
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Bone-marrow-derived microglia: myth or reality?
- 2008
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Ingår i: Current Opinion in Pharmacology. - : Elsevier BV. - 1471-4973 .- 1471-4892. ; 8, s. 508-518
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Tidskriftsartikel (refereegranskat)abstract
- Microglia are the immune cells of the central nervous system (CNS). They patrol the brain environment with their ramifications and they respond quickly in the presence of pathogens and brain damages. Others and we have recently reported the existence of two different types of microglia, the resident and the newly differentiated microglia that are derived from the bone marrow stem cells. Of great interest is the fact that blood-derived microglial cells are associated with amyloid plaques and these cells are able to prevent the formation or eliminate the presence of amyloid deposits in mice that develop the major hallmark of Alzheimer's disease (AD). These cells are also recruited in the brain of other mouse models of brain diseases and acute injuries. They represent, therefore, a fantastic new vehicle for delivering key molecules to improve recovery, repair, and elimination of toxic proteins. However, recent studies have challenged this concept and raised concerns regarding the physiological relevance of bone-marrow-derived microglia. This review discusses both sides of the story and why the models used to follow the phenotypic fate of these cells are so crucial to reach the proper conclusion. Blood-derived progenitors have the ability to populate the CNS, especially during injuries and chronic diseases. However they do not do it in an efficient manner. Such a lack of proper recruitment may explain the delay in recovery and repair after acute damages and accumulation of toxic proteins in chronic brain diseases.
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| 3. |
- Soulet, Denis, et al.
(författare)
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Microglia
- 2008
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Ingår i: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 18:12, s. 506-508
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 4. |
- Soulet, Denis, et al.
(författare)
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Polyamines play a critical role in the control of the innate immune response in the mouse central nervous system
- 2003
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Ingår i: Journal of Cell Biology. - : Rockefeller University Press. - 0021-9525 .- 1540-8140. ; 162:2, s. 257-268
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Tidskriftsartikel (refereegranskat)abstract
- The present work investigated whether polyamines play a role in the control of the innate immune response in the brain. The first evidence that these molecules may be involved in such a process was based on the robust increase in the expression of the first and rate-limiting enzyme of biosynthesis of polyamines during immune stimuli. Indeed, systemic lipopolysaccharide (LPS) administration increased ornithine decarboxylase (ODC) mRNA and protein within neurons and microglia across the mouse central nervous system (CNS). This treatment was also associated with a robust and transient transcriptional activation of genes encoding pro-inflammatory cytokines and toll-like receptor 2 (TLR2) in microglial cells. The endotoxin increased the cerebral activity of ODC, which was abolished by a suicide inhibitor of ODC. The decrease in putrescine levels largely prevented the ability of LPS to trigger tumor necrosis factor alpha and TLR2 gene transcription in the mouse brain. In contrast, expression of both transcripts was clearly exacerbated in response to intracerebral spermine infusion. Finally, inhibition of polyamine synthesis abolished neurodegeneration and increased the survival rate of mice exposed to a model of severe innate immune reaction in the CNS. Thus, polyamines have a major impact on the neuronal integrity and cerebral homeostasis during immune insults.
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| 5. |
- Soulet, Denis, et al.
(författare)
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Role of polyamines in the control of the immune response in the brain
- 2006
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Ingår i: Polyamine cell signaling, Physiology, Pharmacology, and Cancer Research. - Totowa, NJ : Humana Press. - 9781588296252 ; , s. 279-292
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Polyamines are essential polycations involved in a large variety of biological functions, including modulation of the nucleic acid conformation, RNA export and their degradation, protein synthesis, eIF-5A posttranslational modification, signal transduction, cell growth and differentiation, and tumor progression ( 1 –bi3. These various aspects in the biology of polyamines are addressed in other sections of this book.
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