Thus, these data showed that an anti-hypertensive drug has a protective effect against prion-mediated neuronal cell death via autophagy inhibition and AMPK activation, and also suggest that anti-hypertensive drugs may be effective therapeutic agents against neurodegenerative disorders, including prion diseases.
In mouse models, genetic depletion of <i>Cr2</i> causes either a delay or complete prevention of prion disease, but the relative importance of CD35 versus CD21 in promoting prion disease remains unknown.
Although we previously reported that interferon regulatory factor 3 (IRF3) was likely to be involved in the pathogenesis of prion diseases, suggesting the protective role of host innate immune responses mediated by IRF3 signalling, this remained to be clarified.
Thus, these data showed that an anti-hypertensive drug has a protective effect against prion-mediated neuronal cell death via autophagy inhibition and AMPK activation, and also suggest that anti-hypertensive drugs may be effective therapeutic agents against neurodegenerative disorders, including prion diseases.
Those data emphasize a close connection between the prion replication and mitochondrial deacetylation due to SIRT3, thereby partially explaining mitochondrial dysfunction in prion diseases.
These results point to an unexpected function of SARM1 as a regulator of prion-induced neurodegeneration and suggest that XAF1 might constitute a therapeutic target in prion disease.
Thus, these data showed that an anti-hypertensive drug has a protective effect against prion-mediated neuronal cell death via autophagy inhibition and AMPK activation, and also suggest that anti-hypertensive drugs may be effective therapeutic agents against neurodegenerative disorders, including prion diseases.
In the current study, we assessed expression of IFN-I in murine prion disease (ME7) and examined the contribution of the IFN-I receptor IFNAR1 to disease progression.
In addition, several pathways were also identified for specific brain regions, such as REACTOME_CD28_DEPENDENT_PI3K_AKT_SIGNALING (P value = 4.00 × 10<sup>-3</sup> ) for angular gyrus, REACTOME_SIGNALING_BY_CONSTITUTIVELY_ACTIVE_EGFR (P value = 2.22 × 10<sup>-3</sup> ) for anterior caudate, and KEGG_PRION_DISEASES (P value = 1.00 × 10<sup>-4</sup> ) for germinal matrix.
Reactive astrocytes are a prominent feature in the prion disease affected CNS as revealed by distinct morphological changes and upregulation of glial fibrillary acidic protein (GFAP).
In addition, several pathways were also identified for specific brain regions, such as REACTOME_CD28_DEPENDENT_PI3K_AKT_SIGNALING (P value = 4.00 × 10<sup>-3</sup> ) for angular gyrus, REACTOME_SIGNALING_BY_CONSTITUTIVELY_ACTIVE_EGFR (P value = 2.22 × 10<sup>-3</sup> ) for anterior caudate, and KEGG_PRION_DISEASES (P value = 1.00 × 10<sup>-4</sup> ) for germinal matrix.
In addition, several pathways were also identified for specific brain regions, such as REACTOME_CD28_DEPENDENT_PI3K_AKT_SIGNALING (P value = 4.00 × 10<sup>-3</sup> ) for angular gyrus, REACTOME_SIGNALING_BY_CONSTITUTIVELY_ACTIVE_EGFR (P value = 2.22 × 10<sup>-3</sup> ) for anterior caudate, and KEGG_PRION_DISEASES (P value = 1.00 × 10<sup>-4</sup> ) for germinal matrix.
In addition, several pathways were also identified for specific brain regions, such as REACTOME_CD28_DEPENDENT_PI3K_AKT_SIGNALING (P value = 4.00 × 10<sup>-3</sup> ) for angular gyrus, REACTOME_SIGNALING_BY_CONSTITUTIVELY_ACTIVE_EGFR (P value = 2.22 × 10<sup>-3</sup> ) for anterior caudate, and KEGG_PRION_DISEASES (P value = 1.00 × 10<sup>-4</sup> ) for germinal matrix.
Here we show that CD21/35 are high-affinity prion receptors, but mice expressing only CD21 die from prion disease sooner than CD35-expressing mice, which contain less prions early after infection and exhibit delayed terminal disease, likely due to their less organized splenic follicles.
In addition, several pathways were also identified for specific brain regions, such as REACTOME_CD28_DEPENDENT_PI3K_AKT_SIGNALING (P value = 4.00 × 10<sup>-3</sup> ) for angular gyrus, REACTOME_SIGNALING_BY_CONSTITUTIVELY_ACTIVE_EGFR (P value = 2.22 × 10<sup>-3</sup> ) for anterior caudate, and KEGG_PRION_DISEASES (P value = 1.00 × 10<sup>-4</sup> ) for germinal matrix.
In addition, several pathways were also identified for specific brain regions, such as REACTOME_CD28_DEPENDENT_PI3K_AKT_SIGNALING (P value = 4.00 × 10<sup>-3</sup> ) for angular gyrus, REACTOME_SIGNALING_BY_CONSTITUTIVELY_ACTIVE_EGFR (P value = 2.22 × 10<sup>-3</sup> ) for anterior caudate, and KEGG_PRION_DISEASES (P value = 1.00 × 10<sup>-4</sup> ) for germinal matrix.
These results point to an unexpected function of SARM1 as a regulator of prion-induced neurodegeneration and suggest that XAF1 might constitute a therapeutic target in prion disease.
These differentially expressed proteins were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis, which confirmed that the interaction between prion diseases and ECM receptors was the most significant pathways of enrichment.
We assessed the anti-inflammatory and phagocytosis-promoting functions of Del-1 in prion disease and determined whether Del-1 complements Mfge8 in prion clearance in mice with a C57BL/6J genetic background.
Alterations in membrane attachment influence PrPC-associated signaling, and the development of prion disease, yet our knowledge of the role of the GPI-anchor in localization, processing, and function of PrPC in vivo is limited We exchanged the PrPC GPI-anchor signal sequence of for that of Thy-1 (PrPCGPIThy-1) in cells and mice.