Aging brain becomes susceptible to neurodegenerative diseases due to the shifting of microglia and astrocyte phenotypes to an active“pro-inflammatory”state,causing chronic low-grade neuroinflammation.Despite the fac...Aging brain becomes susceptible to neurodegenerative diseases due to the shifting of microglia and astrocyte phenotypes to an active“pro-inflammatory”state,causing chronic low-grade neuroinflammation.Despite the fact that the role of neuroinflammation during aging has been extensively studied in recent years,the underlying causes remain unclear.The identification of relevant proteins and understanding their potential roles in neuroinflammation can help explain their potential of becoming biomarkers in the aging brain and as drug targets for prevention and treatment.This will eventually reduce the chances of developing neurodegenerative diseases and promote healthier lives in the elderly.In this review,we have summarized the morphological and cellular changes in the aging brain,the effects of age-related neuroinflammation,and the potential role of cofilin-1 during neuroinflammation.We also discuss other factors contributing to brain aging and neuroinflammation.展开更多
Actin is the principal component of the cytoskeleton, a structure that can be disassembled and reassem-bled in a matter of seconds in vivo. The state of assembly of actin in vivo is primarily regulated by one ormore a...Actin is the principal component of the cytoskeleton, a structure that can be disassembled and reassem-bled in a matter of seconds in vivo. The state of assembly of actin in vivo is primarily regulated by one ormore actin binding proteins (ABPs). Typically, the actions of ABPs have been studied one by one, however,we propose that multiple ABPs, acting cooperatively, may be involved in the control of actin filament length.Cofilin and DNase I are two ABPs that have previously been demonstrated to form a ternary complex withactin in vitro. This is the first report to demonstrate their co-localisation in vivo, and differences in theirdistributions. Our observations strongly suggest a physiological role for higher order complexes of actin inregulation of cytoskeletal assembly during processes such as cell division.展开更多
As a fundamental component of the host cellular cytoskeleton, actin is routinely engaged by infecting viruses. Furthermore, viruses from diverse groups, and infecting diverse hosts, have convergently evolved an array ...As a fundamental component of the host cellular cytoskeleton, actin is routinely engaged by infecting viruses. Furthermore, viruses from diverse groups, and infecting diverse hosts, have convergently evolved an array of mechanisms for manipulating the actin cytoskeleton for efficacious infection. An ongoing chorus of research now indicates that the actin cytoskeleton is critical for viral replication at many stages of the viral life cycle, including binding, entry, nuclear localization, genomic transcription and reverse transcription, assembly, and egress/dissemination. Specifically, viruses subvert the force-generating and macromolecular scaffolding properties of the actin cytoskeleton to propel viral surfing, internalization, and migration within the cell. Additionally, viruses utilize the actin cytoskeleton to support and organize assembly sites, and eject budding virions for cell-to-cell transmission. It is the purpose of this review to provide an overview of current research, focusing on the various mechanisms and themes of virus-mediated actin modulation described therein.展开更多
F-actins are semi-flexible polyelectrolytes and can be assembled into large polymer-actin complex with polymorphism through electrostatic interaction with polycations. This study investigates the structural phase beha...F-actins are semi-flexible polyelectrolytes and can be assembled into large polymer-actin complex with polymorphism through electrostatic interaction with polycations. This study investigates the structural phase behavior and the growth of polymer-actin complexes in terms of its longitudinal and lateral sizes. Our results show that formation of polymer-actin complexes is cooperative, and morphology and growth of polymer-actin complexes depend on polycation species and concentrations of polycation and salt in a constant actin concentration. We found that the longitudinal growth and lateral growth of polymer-actin complexes are dominated by different factors. This induces the structural polymorphism of polymer-actin complexes. Major factors to influence the polymorphism of polymer-actin complexes in polyelectrolytc system have been discussed. Our results indicate that the semi-flexible polyelectrolyte nature of F-actins is important for controlling the morphology and growth ofactin architectures in cell.展开更多
Actin is the principal component of the cytoskeleton, a structure that can be disassembled and reassembled in a matter of seconds in vivo. The state of assembly of actin in vivo is primarily regulated by one or more a...Actin is the principal component of the cytoskeleton, a structure that can be disassembled and reassembled in a matter of seconds in vivo. The state of assembly of actin in vivo is primarily regulated by one or more actin binding proteins (ABPs). Typically, the actions of ABPs have been studied one by one, however, we propose that multiple ABPs, acting cooperatively, may be involved in the control of actin filament length. Cofilin and DNase I are two ABPs that have previously been demonstrated to form a ternary complex with actin in vitro. This is the first report to demonstrate their co-localisation in vivo, and differences in their distributions. Our observations strongly suggest a physiological role for higher order complexes of actin in regulation of cytoskeletal assembly during processes such as cell division.展开更多
Cofilin is a low molecular weight actin-binding protein widely found in eukaryotic cells in ADF/cofilin family proteins,which has a wide range of biological effects and has gradually become a research hotspot in recen...Cofilin is a low molecular weight actin-binding protein widely found in eukaryotic cells in ADF/cofilin family proteins,which has a wide range of biological effects and has gradually become a research hotspot in recent years.We review the structural characteristics of cofilin,the mechanism of regulating actin,biological functions,and the relationship with clinical diseases to explore its role in the development of cancer,nervous system diseases,osteoarthritis,heart and kidney diseases.The use of cofilin phosphorylation pathways as major action-targeting sites in the treatment of these diseases could provide a basis for the development of new drugs,such as Rho related protein kinases inhibitors netarsudil to prevent cancer metastasis,neuroligin C-terminal domain(NLG1-CTD)peptides with high affinity to inhibit LIM kinase thereby preventing nervous system diseases,grape seed proanthocyanidins to inhibit cofilin related oxidative stress in the treatment of heart and kidney diseases.展开更多
基金supported by Fellowship from Saudi Arabia Cultural Mission,College of Pharmacy,Department of Pharmaceutical Chemistry,King Saud University,Riyadh,Saudi Arabia
文摘Aging brain becomes susceptible to neurodegenerative diseases due to the shifting of microglia and astrocyte phenotypes to an active“pro-inflammatory”state,causing chronic low-grade neuroinflammation.Despite the fact that the role of neuroinflammation during aging has been extensively studied in recent years,the underlying causes remain unclear.The identification of relevant proteins and understanding their potential roles in neuroinflammation can help explain their potential of becoming biomarkers in the aging brain and as drug targets for prevention and treatment.This will eventually reduce the chances of developing neurodegenerative diseases and promote healthier lives in the elderly.In this review,we have summarized the morphological and cellular changes in the aging brain,the effects of age-related neuroinflammation,and the potential role of cofilin-1 during neuroinflammation.We also discuss other factors contributing to brain aging and neuroinflammation.
基金We would like to thank Dr. Neil Nosworthy forsupplying his expertise with the native PAGE. This work was supported by grants from the Australian Research Council and the Ramaciotti Foundation.
文摘Actin is the principal component of the cytoskeleton, a structure that can be disassembled and reassem-bled in a matter of seconds in vivo. The state of assembly of actin in vivo is primarily regulated by one ormore actin binding proteins (ABPs). Typically, the actions of ABPs have been studied one by one, however,we propose that multiple ABPs, acting cooperatively, may be involved in the control of actin filament length.Cofilin and DNase I are two ABPs that have previously been demonstrated to form a ternary complex withactin in vitro. This is the first report to demonstrate their co-localisation in vivo, and differences in theirdistributions. Our observations strongly suggest a physiological role for higher order complexes of actin inregulation of cytoskeletal assembly during processes such as cell division.
基金supported by US Public Health Service grant 1R01MH102144 from NIMH to Y. W
文摘As a fundamental component of the host cellular cytoskeleton, actin is routinely engaged by infecting viruses. Furthermore, viruses from diverse groups, and infecting diverse hosts, have convergently evolved an array of mechanisms for manipulating the actin cytoskeleton for efficacious infection. An ongoing chorus of research now indicates that the actin cytoskeleton is critical for viral replication at many stages of the viral life cycle, including binding, entry, nuclear localization, genomic transcription and reverse transcription, assembly, and egress/dissemination. Specifically, viruses subvert the force-generating and macromolecular scaffolding properties of the actin cytoskeleton to propel viral surfing, internalization, and migration within the cell. Additionally, viruses utilize the actin cytoskeleton to support and organize assembly sites, and eject budding virions for cell-to-cell transmission. It is the purpose of this review to provide an overview of current research, focusing on the various mechanisms and themes of virus-mediated actin modulation described therein.
基金This research is financially supported by SORST, JST and the Ministry of Education, Science, Sports, and Culture, Japan (Grant-in-Aid of Creative Scientific Research).
文摘F-actins are semi-flexible polyelectrolytes and can be assembled into large polymer-actin complex with polymorphism through electrostatic interaction with polycations. This study investigates the structural phase behavior and the growth of polymer-actin complexes in terms of its longitudinal and lateral sizes. Our results show that formation of polymer-actin complexes is cooperative, and morphology and growth of polymer-actin complexes depend on polycation species and concentrations of polycation and salt in a constant actin concentration. We found that the longitudinal growth and lateral growth of polymer-actin complexes are dominated by different factors. This induces the structural polymorphism of polymer-actin complexes. Major factors to influence the polymorphism of polymer-actin complexes in polyelectrolytc system have been discussed. Our results indicate that the semi-flexible polyelectrolyte nature of F-actins is important for controlling the morphology and growth ofactin architectures in cell.
文摘Actin is the principal component of the cytoskeleton, a structure that can be disassembled and reassembled in a matter of seconds in vivo. The state of assembly of actin in vivo is primarily regulated by one or more actin binding proteins (ABPs). Typically, the actions of ABPs have been studied one by one, however, we propose that multiple ABPs, acting cooperatively, may be involved in the control of actin filament length. Cofilin and DNase I are two ABPs that have previously been demonstrated to form a ternary complex with actin in vitro. This is the first report to demonstrate their co-localisation in vivo, and differences in their distributions. Our observations strongly suggest a physiological role for higher order complexes of actin in regulation of cytoskeletal assembly during processes such as cell division.
基金This work is supported by the General Research Project of Zhejiang Education Department(No.Y202044448).
文摘Cofilin is a low molecular weight actin-binding protein widely found in eukaryotic cells in ADF/cofilin family proteins,which has a wide range of biological effects and has gradually become a research hotspot in recent years.We review the structural characteristics of cofilin,the mechanism of regulating actin,biological functions,and the relationship with clinical diseases to explore its role in the development of cancer,nervous system diseases,osteoarthritis,heart and kidney diseases.The use of cofilin phosphorylation pathways as major action-targeting sites in the treatment of these diseases could provide a basis for the development of new drugs,such as Rho related protein kinases inhibitors netarsudil to prevent cancer metastasis,neuroligin C-terminal domain(NLG1-CTD)peptides with high affinity to inhibit LIM kinase thereby preventing nervous system diseases,grape seed proanthocyanidins to inhibit cofilin related oxidative stress in the treatment of heart and kidney diseases.
