Recent findings have implicated inflammatory responses in the central nervous system in a variety of neuropsychiatric and neurodegenerative diseases,and the understanding and control of immunological responses could b...Recent findings have implicated inflammatory responses in the central nervous system in a variety of neuropsychiatric and neurodegenerative diseases,and the understanding and control of immunological responses could be a major factor of future therapeutic strategies for neurological disorders.Microglia,derived from myelogenous cells,respond to a number of stimuli and make immune responses,resulting in a prominent role as cells that act on inflammation in the central nervous system.Fractalkine(FKN or CX3CL1)signaling is an important factor that influences the inflammatory response of microglia.The receptor for FKN,CX3CR1,is usually expressed in microglia in the brain,and therefore the inflammatory response of microglia is modified by FKN.Reportedly,FKN often suppresses inflammatory responses in microglia and activation of its receptor may be effective in the treatment of inflammatory neurological disorders.However,it has also been suggested that inflammatory responses facilitated by FKN signaling aggravate neurological disorders.Thus,further studies are still required to resolve the conflicting interpretation of the protective or deleterious contribution of microglial FKN signaling.Yet notably,regulation of FKN signaling has recently been shown to be beneficial in the treatment of human diseases,although not neurological diseases.In addition,a CX3CR1 inhibitor has been developed and successfully tested in animal models,and it is expected to be in human clinical trials in the future.In this review,I describe the potential therapeutic consideration of microglial CX3CR1 dynamics through altered FKN signaling.展开更多
As recent medical progress decreases the incidence of certain diseases, ischemic brain injury remains one of the major dis- eases that threaten human lives, especially in western countries. Ischemic brain injury occur...As recent medical progress decreases the incidence of certain diseases, ischemic brain injury remains one of the major dis- eases that threaten human lives, especially in western countries. Ischemic brain injury occurs as a result of lack of oxygen and nutrients due to obstruction of blood flow in the brain, and often leads to neurological disorders such as cerebral palsy, depression, and ultimately, death. Around 800,000 Americans suffer a new or recurrent stroke, and more than 130,000 people die annually in the United States （Goldstein et al., 2011）. Despite much effort in searching for an effective treatment, at most a few reagents are approved for therapeutic medication in many countries.展开更多
基金supported by a KAKENHI Grant-in-Aid for Scientific Research,No.21K09133(to KI).
文摘Recent findings have implicated inflammatory responses in the central nervous system in a variety of neuropsychiatric and neurodegenerative diseases,and the understanding and control of immunological responses could be a major factor of future therapeutic strategies for neurological disorders.Microglia,derived from myelogenous cells,respond to a number of stimuli and make immune responses,resulting in a prominent role as cells that act on inflammation in the central nervous system.Fractalkine(FKN or CX3CL1)signaling is an important factor that influences the inflammatory response of microglia.The receptor for FKN,CX3CR1,is usually expressed in microglia in the brain,and therefore the inflammatory response of microglia is modified by FKN.Reportedly,FKN often suppresses inflammatory responses in microglia and activation of its receptor may be effective in the treatment of inflammatory neurological disorders.However,it has also been suggested that inflammatory responses facilitated by FKN signaling aggravate neurological disorders.Thus,further studies are still required to resolve the conflicting interpretation of the protective or deleterious contribution of microglial FKN signaling.Yet notably,regulation of FKN signaling has recently been shown to be beneficial in the treatment of human diseases,although not neurological diseases.In addition,a CX3CR1 inhibitor has been developed and successfully tested in animal models,and it is expected to be in human clinical trials in the future.In this review,I describe the potential therapeutic consideration of microglial CX3CR1 dynamics through altered FKN signaling.
文摘As recent medical progress decreases the incidence of certain diseases, ischemic brain injury remains one of the major dis- eases that threaten human lives, especially in western countries. Ischemic brain injury occurs as a result of lack of oxygen and nutrients due to obstruction of blood flow in the brain, and often leads to neurological disorders such as cerebral palsy, depression, and ultimately, death. Around 800,000 Americans suffer a new or recurrent stroke, and more than 130,000 people die annually in the United States （Goldstein et al., 2011）. Despite much effort in searching for an effective treatment, at most a few reagents are approved for therapeutic medication in many countries.
