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The brain displays a unique IFNAR expression profile whereby IFNAR1 is readily expressed but the IFNAR2 subunit is scarce, indicating that peripheral type 1 IFN ARQ 197 製造者 signalling differs from the CNS. Indeed IFNB can sig nal independent of IFNAR2, which considering the known receptor subunit imbalance, is crucial to potential signalling in the brain. These observations highlight that targeting IFNAR1 alone is a useful tool in controlling type 1 IFN signalling in the brain and we hypothesise that therapeutic modulation of this receptor shall prove benefi cial in hypoxia ischaemia injury outcome. However type 1 IFN signalling is crucial in the regulation of innate immunity, critical in viral immunity, beneficial inflam matory responses and protection from autoimmune dis ease such as experimental autoimmune encephalomyelitis.<br><br> In conditions of brain hypoxia ischaemia, activation of innate immune system is required for microglia to suc cessfully remove cellular debris from the inflamed envir onment and this process is largely considered protective. Inhibiting IFNAR1 dependent signalling AZD0530 構造 may induce cen tral immuno suppression, which renders this reparative clearance mechanism inactive, perpetuating tissue damage and increasing penumbra size. It is clear that timing, de gree of modulation, and, cell type specificity are key fac tors in determining the potential therapeutic benefit of modulating IFNAR1. This study proposes that modulation of neuronal IFNAR1 levels or activity may be beneficial in controlling cellular damage following hypoxia ischaemia injuries.<br><br> Neuro inflammation is a double edged sword. A deli cate balance exists between a protective clearance role, where inflammation is resolved, and a deleterious role where unresolved inflammatory processes drive cell death. We hypothesise that type 1 IFN signalling is a key process in controlling this neuro inflammatory environ ment and contributes to the deleterious weight of Alvocidib ic50 the neuro inflammatory fulcrum. We further propose that modulating type 1 IFN production and or signalling in the CNS may enable beneficial immune modulation and improve physiological outcome. Clearly a greater body of knowledge of the neuro inflammatory cascades gov erning neuro degeneration in hypoxic ischaemic injuries is required, however our study supports targeting type 1 IFN signalling as a novel therapeutic strategy.<br><br> Parkinsons disease is the second most common neurodegenerative disease characterized by a dramatic loss of dopaminergic neurons in substantia nigra. Although the etiology of PD and the underlying mechanisms for disease development remain incompletely understood, increasing evidence has suggested that inflammatory processes play a key role in the pathogenesis of PD. Microglia are the resident macrophages of the central nervous system and act as the prime effector cells in mediating neuroinflammation. It has been suggested that inflammatory mediators such as nitric oxide, TNF, and IL 1B derived from microglia are involving in the progression of neuronal cell death in PD. Indeed, lipopolysaccharide as an inflammation elicitor has often been used to generate phenotypes of PD in animals.