In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of A...In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.展开更多
[Objective]The aim was to prove that the mitochondrial genes of Cyt b and 12S rRNA with different evolutional rates have effects on the topological structures of phylogenetic trees.[Method]The complete sequences of Cy...[Objective]The aim was to prove that the mitochondrial genes of Cyt b and 12S rRNA with different evolutional rates have effects on the topological structures of phylogenetic trees.[Method]The complete sequences of Cyt b and 12S rRNA from 15 species in 12 families of snakes were downloaded and extracted from GenBank,while their molecular phylogenetic trees were constructed by Maximum Likelihood（ML） method with GTR ＋I ＋G substitute model based on PAUP4.0 software.[Result]With the same software,methods and species,the difference in topological structures of phylogenetic trees was mainly due to different evolutional rates of Cyt b and 12S rRNA genes.[Conclusion]In studies on phylogenetic trees,aimed to different research species and purposes,phylogenetic trees should be constructed by choosing the correct and appropriate genes.展开更多
基金supported by STI2030-Major Projects,No.2021ZD 0201801(to JG)Shanxi Province Basic Research Program,No.20210302123429(to QS).
文摘In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.
基金Supported by Natural Science Fund in Guangdong(915102600100-0003)Project for Excellent Young Scientists and Engineers in Guangdong Academy of Sciences(200804)Fund of Open Laboratory for Protection and Utilization of Wildlife in Guangdong(200901)~~
文摘[Objective]The aim was to prove that the mitochondrial genes of Cyt b and 12S rRNA with different evolutional rates have effects on the topological structures of phylogenetic trees.[Method]The complete sequences of Cyt b and 12S rRNA from 15 species in 12 families of snakes were downloaded and extracted from GenBank,while their molecular phylogenetic trees were constructed by Maximum Likelihood（ML） method with GTR ＋I ＋G substitute model based on PAUP4.0 software.[Result]With the same software,methods and species,the difference in topological structures of phylogenetic trees was mainly due to different evolutional rates of Cyt b and 12S rRNA genes.[Conclusion]In studies on phylogenetic trees,aimed to different research species and purposes,phylogenetic trees should be constructed by choosing the correct and appropriate genes.
