Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals.Inflammasome multiprotein complexes are composed of thr...Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals.Inflammasome multiprotein complexes are composed of three parts:a sensor protein,an adaptor,and pro-caspase-1.Activation of the inflammasome leads to the activation of caspase-1,which cleaves pro-inflammatory cytokines such as IL-ip and IL-18,leading to pyroptosis.Effectors of the inflammasome not only provide protection against infectious pathogens,but also mediate control over sterile insults.Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases,cancer,and neurodegenerative disorders.Here,we review the role of the inflammasome as a double-edged sword in various diseases,and the outcomes can be either good or bad depending on the disease,as well as the genetic background.We highlight inflammasome memory and the two-shot activation process.We also propose the M-and N-type inflammation model,and discuss how the inflammasome pathway may be targeted for the development of novel therapy.展开更多
The ribosome is a multi-unit complex that translates mRNA into protein.Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation,differentiation,apoptosis,developmen...The ribosome is a multi-unit complex that translates mRNA into protein.Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation,differentiation,apoptosis,development,and transformation.The mTORC1,Myc,and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis.Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth.Myc is implicated in cancer development by enhancing RNA Pol II activity,leading to uncontrolled cancer cell growth.The deregulation of noncoding RNAs such as microRNAs,long noncoding RNAs,and circular RNAs is involved in developing blood,neurodegenerative diseases,and atherosclerosis.We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance.We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting,ribosome-stalling,and ribosome-collision.We summarize the role of ribosome biogenesis in the development of various diseases.Furthermore,we review the current clinical trials,prospective vaccines for COVID-19,and therapies targeting ribosome biogenesis in cancer,cardiovascular disease,aging,and neurodegenerative disease.展开更多
基金This work was supported by the National Natural Science Foundation of China(81870194 and 91849122 to Y.L.,81873528 and 81670358 to Y.-H.S.,91839101 to Z.S.,and U1601227 to X.-Y.Y.)Jiangsu Province Peak of Talent in Six Industries(BU24600117 to Y.L.)Introduction Project of Clinical Medicine Expert Team for Suzhou(No.SZYJTD201704).
文摘Inflammasomes are protein complexes of the innate immune system that initiate inflammation in response to either exogenous pathogens or endogenous danger signals.Inflammasome multiprotein complexes are composed of three parts:a sensor protein,an adaptor,and pro-caspase-1.Activation of the inflammasome leads to the activation of caspase-1,which cleaves pro-inflammatory cytokines such as IL-ip and IL-18,leading to pyroptosis.Effectors of the inflammasome not only provide protection against infectious pathogens,but also mediate control over sterile insults.Aberrant inflammasome signaling has been implicated in the development of cardiovascular and metabolic diseases,cancer,and neurodegenerative disorders.Here,we review the role of the inflammasome as a double-edged sword in various diseases,and the outcomes can be either good or bad depending on the disease,as well as the genetic background.We highlight inflammasome memory and the two-shot activation process.We also propose the M-and N-type inflammation model,and discuss how the inflammasome pathway may be targeted for the development of novel therapy.
基金This work was supported by the National Natural Science Foundation of China(NSFC,No.81870194 to Y.Li,No.91849122 to Y.Li,NSFC,Nos.81873528,81670358 to Y.-H.S.,No.U1601227 to X.-Y.Y.)Jiangsu Province Peak of Talent in Six Industries(BU24600117 to Y.Li.)+6 种基金the project for the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD),and Translational Research Grant of NCRCH(2020WSB07)The Introduction Project of Clinical Medicine Expert Team for Suzhou(No.SZYJTD201704)The Fundamental Research Funds for the Central Universities(2019PT350005 to X.P.)National Natural Science Foundation of China(81970444 to X.P.)Beijing Municipal Science and Technology Project(Z201100005420030 to X.P.)National high-level talents special support plan(2020-RSW02 to X.P.)CAMS Innovation Fund for Medical Sciences(2021-I2M-1-065 to X.P.).We apologize in advance to colleagues whose work was not directly cited in this Review because of space limitations.
文摘The ribosome is a multi-unit complex that translates mRNA into protein.Ribosome biogenesis is the process that generates ribosomes and plays an essential role in cell proliferation,differentiation,apoptosis,development,and transformation.The mTORC1,Myc,and noncoding RNA signaling pathways are the primary mediators that work jointly with RNA polymerases and ribosome proteins to control ribosome biogenesis and protein synthesis.Activation of mTORC1 is required for normal fetal growth and development and tissue regeneration after birth.Myc is implicated in cancer development by enhancing RNA Pol II activity,leading to uncontrolled cancer cell growth.The deregulation of noncoding RNAs such as microRNAs,long noncoding RNAs,and circular RNAs is involved in developing blood,neurodegenerative diseases,and atherosclerosis.We review the similarities and differences between eukaryotic and bacterial ribosomes and the molecular mechanism of ribosome-targeting antibiotics and bacterial resistance.We also review the most recent findings of ribosome dysfunction in COVID-19 and other conditions and discuss the consequences of ribosome frameshifting,ribosome-stalling,and ribosome-collision.We summarize the role of ribosome biogenesis in the development of various diseases.Furthermore,we review the current clinical trials,prospective vaccines for COVID-19,and therapies targeting ribosome biogenesis in cancer,cardiovascular disease,aging,and neurodegenerative disease.
