Prion diseases are fatal neurodegenerative conditions with highly accurate CSF and imaging diagnostic tests, but major unmet needs for blood biomarkers. Using ultrasensitive immuno-assays, we measured tau and neurofilament light chain (NfL) protein concentrations in 709 plasma samples taken from 377 individuals with prion disease during a 12 year prospective clinical study, alongside healthy and neurological control groups. This provides an unprecedented opportunity to evaluate their potential as biomarkers.
View Article and Find Full Text PDFThis chapter examines the use of proteomics in understanding pathogenesis and identifying possible biomarkers in a range of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and prion diseases. We have attempted to look at the neuroproteomic approach from a biomarker discovery point of view. Novel biomarkers can pave the way for new therapeutic targets and lead us to a better understanding of the pathogenesis involved in the neurodegenerative diseases.
View Article and Find Full Text PDFUnlabelled: Carbon nanotubes (CNTs) have promised a range of applications in biomedicine. Although influenced by the dispersants used, CNTs are recognized by the innate immune system, predominantly by the classical pathway of the complement system. Here, we confirm that complement activation by the CNT used continues up to C3 and C5, indicating that the entire complement system is activated including the formation of membrane-attack complexes.
View Article and Find Full Text PDFProperdin and factor H are two key regulatory proteins having opposite functions in the alternative complement pathway. Properdin up-regulates the alternative pathway by stabilizing the C3bBb complex, whereas factor H downregulates the pathway by promoting proteolytic degradation of C3b. While factor H is mainly produced in the liver, there are several extrahepatic sources.
View Article and Find Full Text PDFSurfactant proteins SP-A and SP-D are hydrophilic, collagen-containing calcium-dependent lectins, which appear to have a range of innate immune functions at pulmonary as well as extrapulmonary sites. These proteins bind to target ligands on pathogens, allergens, and apoptotic cells, via C-terminal homotrimeric carbohydrate recognition domains, while the collagen region brings about the effector functions via its interaction with cell surface receptors. SP-A and SP-D deal with various pathogens, using a range of innate immune mechanisms such as agglutination/aggregation, enhancement of phagocytosis, and killing mechanisms by phagocytic cells and direct growth inhibition.
View Article and Find Full Text PDFFront Biosci (Elite Ed)
January 2012
Innate immunity mediated by pattern recognition proteins is relevant in the host defense against fungi. SP-A and SP-D are two such proteins belonging to the class of collagen domain containing C-type lectins, or collectins. They bind to the sugar moieties present on the cell walls of various fungi in a dose dependent manner via their carbohydrate recognition domain (CRD).
View Article and Find Full Text PDFHuntington's disease (HD) is a progressive neurodegenerative disorder that is caused by abnormal expansion of CAG trinucleotide repeats. Neuroinflammation is a typical feature of most neurodegenerative diseases that leads to an array of pathological changes within the affected areas in the brain. The neurodegeneration in HD is also caused by aberrant immune response in the presence of aggregated mutant huntingtin protein.
View Article and Find Full Text PDFC1q is a versatile innate immune molecule that serves as the initiation subcomponent of the classical complement pathway. In addition, it is also a potent pattern recognition molecule, the versatility of which has fuelled its functional flexibility. C1q recognises an array of self, non-self and altered-self ligands.
View Article and Find Full Text PDFPulmonary surfactant proteins, SP-A and SP-D, are carbohydrate pattern recognition molecules of innate immunity, which significantly enhance phagocytosis and killing of Aspergillus fumigatus, a pathogenic fungus, by neutrophils and macrophages. The present study examined the susceptibility of immunosuppressed SP-A gene deficient (SP-A(-/-)) or SP-D gene deficient (SP-D(-/-)) mice to A. fumigatus conidia challenge compared to wild-type (WT) mice.
View Article and Find Full Text PDFC1q, the ligand recognition subcomponent of the classical complement pathway has steadily been gaining recognition as a bridge between innate and adaptive immunity. C1q has been shown to be involved in the modulation of various immune cells (such as dendritic cells, platelets, microglia cells and lymphocytes), clearance of apoptotic cells, a range of cell processes such as differentiation, chemotaxis, aggregation and adhesion, and pathogenesis of neurodegenerative diseases and systemic lupus erythematosus. Recent studies have highlighted the importance of C1q during pregnancy, coagulation process and embryonic development including neurological synapse function.
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