Protein quality control involves many processes that jointly act to regulate the expression, localization, turnover, and degradation of proteins, and has been highlighted in recent studies as critical to the different...Protein quality control involves many processes that jointly act to regulate the expression, localization, turnover, and degradation of proteins, and has been highlighted in recent studies as critical to the differentiation of stem cells during regeneration. The roles of constitutively secreted extracellular chaperones in neuronal injury and disease are poorly understood. Extracellular chaperones are multifunctional proteins expressed by many cell types, including those of the nervous system, known to facilitate protein quality control processes. These molecules exert pleiotropic effects and have been implicated as playing important protective roles in a variety of stress conditions, including tissue damage, infections, and local tissue inflammation. This article aims to provide a critical review of what is currently known about the functions of extracellular chaperones in neuronal repair and regeneration and highlight future directions for this important research area. We review what is known of four constitutively secreted extracellular chaperones directly implicated in processes of neuronal damage and repair, including transthyretin, clusterin, α2-macroglobulin, and neuroserpin, and propose that investigation into the effects of these and other extracellular chaperones on neuronal repair and regeneration has the potential to yield valuable new therapies.展开更多
The worldwide decline over the last decade in the number of clinical cases of malaria does not mean an end to the universal problem of malaria pathogenesis in those afflicted by infection. Resistance to drugs, higher ...The worldwide decline over the last decade in the number of clinical cases of malaria does not mean an end to the universal problem of malaria pathogenesis in those afflicted by infection. Resistance to drugs, higher risk of disease relapse and failure to maintain effective memory of the pathogen in the absence of persistent exposure result in the repeated failure of anti-malarialtreatments. The artificial blocking of transmission of the Plasmodium parasite between hosts from human to Anopheles mosquito, and vice versa, is crucial to restricting the spread of disease. However, a limited knowledge of the molecular mechanisms in operation for transmission of malaria has impeded progress towards a transmission-blocking vaccine. This review highlights the role of anti-malarial immune responses to antigen-specific targets for designing effective vaccines against the sexual stages of Plasmodium that occur within the invertebrate vector. In particular, artificial induction of gametocyte and ookinete apoptosis as a novel means to prevent gamete fertilization and oocyte development, respectively, is highlighted. This and other recent insights into our understanding of the molecular regulation of transmission-blocking immunity are discussed and future prospects considered.展开更多
文摘Protein quality control involves many processes that jointly act to regulate the expression, localization, turnover, and degradation of proteins, and has been highlighted in recent studies as critical to the differentiation of stem cells during regeneration. The roles of constitutively secreted extracellular chaperones in neuronal injury and disease are poorly understood. Extracellular chaperones are multifunctional proteins expressed by many cell types, including those of the nervous system, known to facilitate protein quality control processes. These molecules exert pleiotropic effects and have been implicated as playing important protective roles in a variety of stress conditions, including tissue damage, infections, and local tissue inflammation. This article aims to provide a critical review of what is currently known about the functions of extracellular chaperones in neuronal repair and regeneration and highlight future directions for this important research area. We review what is known of four constitutively secreted extracellular chaperones directly implicated in processes of neuronal damage and repair, including transthyretin, clusterin, α2-macroglobulin, and neuroserpin, and propose that investigation into the effects of these and other extracellular chaperones on neuronal repair and regeneration has the potential to yield valuable new therapies.
文摘The worldwide decline over the last decade in the number of clinical cases of malaria does not mean an end to the universal problem of malaria pathogenesis in those afflicted by infection. Resistance to drugs, higher risk of disease relapse and failure to maintain effective memory of the pathogen in the absence of persistent exposure result in the repeated failure of anti-malarialtreatments. The artificial blocking of transmission of the Plasmodium parasite between hosts from human to Anopheles mosquito, and vice versa, is crucial to restricting the spread of disease. However, a limited knowledge of the molecular mechanisms in operation for transmission of malaria has impeded progress towards a transmission-blocking vaccine. This review highlights the role of anti-malarial immune responses to antigen-specific targets for designing effective vaccines against the sexual stages of Plasmodium that occur within the invertebrate vector. In particular, artificial induction of gametocyte and ookinete apoptosis as a novel means to prevent gamete fertilization and oocyte development, respectively, is highlighted. This and other recent insights into our understanding of the molecular regulation of transmission-blocking immunity are discussed and future prospects considered.
