Alzheimer’s disease(AD) is an age-related neurodegenerative disease characterized by progressive cognitive defects. The role of the central immune system dominated by microglia in the progression of AD has been exten...Alzheimer’s disease(AD) is an age-related neurodegenerative disease characterized by progressive cognitive defects. The role of the central immune system dominated by microglia in the progression of AD has been extensively investigated. However, little is known about the peripheral immune system in AD pathogenesis.Recently, with the discovery of the meningeal lymphatic vessels and glymphatic system, the roles of the acquired immunity in the maintenance of central homeostasis and neurodegenerative diseases have attracted an increasing attention. The T cells not only regulate the function of neurons, astrocytes, microglia, oligodendrocytes and brain microvascular endothelial cells, but also participate in the clearance of β-amyloid(Aβ) plaques. Apart from producing antibodies to bind Aβ peptides, the B cells affect Aβ-related cascades via a variety of antibodyindependent mechanisms. This review systemically summarizes the recent progress in understanding pathophysiological roles of the T cells and B cells in AD.展开更多
With the increase in the aging population,the global number of people with Alzheimer’s disease(AD)progressively increased worldwide.The situation is aggravated by the fact that there is no the efective pharmacologica...With the increase in the aging population,the global number of people with Alzheimer’s disease(AD)progressively increased worldwide.The situation is aggravated by the fact that there is no the efective pharmacological therapy of AD.Photobiomodulation(PBM)is non-pharmacological approach that has shown very promising results in the therapy of AD in pilot clinical and animal studies.However,the mechanisms of therapeutic efects of PBM for AD are poorly understood.In this study on mice,we demonstrate that photodynamic efects of 5-aminolevulenic acid and laser 635 nm cause reduction of network of the meningeal lymphatic vessels(MLVs)leading to suppression of lymphatic removal of beta-amyloid(Aβ)from the right lateral ventricle and the hippocampus.Using the original protocol of PBM under electroencephalographic monitoring of wakefulness and sleep stages in non-anesthetized mice,we discover that the 7-day course of PBM during deep sleep vs.wakefulness provides better restoration of clearance of Aβfrom the ventricular system of the brain and the hippocampus.Our results shed light on the mechanism of PBM and show the stimulating efects of PBM on the brain lymphatic drainage that promotes transport of Aβvia the lymphatic pathway.The efects of PBM on the brain lymphatics in sleeping brain open a new niche in the study of restorative functions of sleep as well as it is an important informative platform for the development of innovative smart sleep technologies for the therapy of AD.展开更多
基金supported by grants from the National Natural Science Foundation of China (Grants No. 82071199 and 32100674)。
文摘Alzheimer’s disease(AD) is an age-related neurodegenerative disease characterized by progressive cognitive defects. The role of the central immune system dominated by microglia in the progression of AD has been extensively investigated. However, little is known about the peripheral immune system in AD pathogenesis.Recently, with the discovery of the meningeal lymphatic vessels and glymphatic system, the roles of the acquired immunity in the maintenance of central homeostasis and neurodegenerative diseases have attracted an increasing attention. The T cells not only regulate the function of neurons, astrocytes, microglia, oligodendrocytes and brain microvascular endothelial cells, but also participate in the clearance of β-amyloid(Aβ) plaques. Apart from producing antibodies to bind Aβ peptides, the B cells affect Aβ-related cascades via a variety of antibodyindependent mechanisms. This review systemically summarizes the recent progress in understanding pathophysiological roles of the T cells and B cells in AD.
基金We thank research center“Symbiosis”and immunochemistry laboratory IBPPM RAS for their support with immunofuorescence analysis and confocal microscopy within Project No.GR 121031100266-3SGO,FI,SA,BI,TA,DA,ZM,ED,AV,EA,VV,TA,KV,MM,and MA were supported by grant(No.23-75-30001)+1 种基金the Russian Science Foundation,DA and ED were supported by Grant(No.21-75-10088)the Russian Science Foundation and by Grant from the Russian Ministry of Science and High Education(No.075-15-2022-1094).
文摘With the increase in the aging population,the global number of people with Alzheimer’s disease(AD)progressively increased worldwide.The situation is aggravated by the fact that there is no the efective pharmacological therapy of AD.Photobiomodulation(PBM)is non-pharmacological approach that has shown very promising results in the therapy of AD in pilot clinical and animal studies.However,the mechanisms of therapeutic efects of PBM for AD are poorly understood.In this study on mice,we demonstrate that photodynamic efects of 5-aminolevulenic acid and laser 635 nm cause reduction of network of the meningeal lymphatic vessels(MLVs)leading to suppression of lymphatic removal of beta-amyloid(Aβ)from the right lateral ventricle and the hippocampus.Using the original protocol of PBM under electroencephalographic monitoring of wakefulness and sleep stages in non-anesthetized mice,we discover that the 7-day course of PBM during deep sleep vs.wakefulness provides better restoration of clearance of Aβfrom the ventricular system of the brain and the hippocampus.Our results shed light on the mechanism of PBM and show the stimulating efects of PBM on the brain lymphatic drainage that promotes transport of Aβvia the lymphatic pathway.The efects of PBM on the brain lymphatics in sleeping brain open a new niche in the study of restorative functions of sleep as well as it is an important informative platform for the development of innovative smart sleep technologies for the therapy of AD.
