Chronic inflammation has increasingly been acknowledged as a hallmark feature of several progressive neurodegenerative disorders. Accruing evidence indicates that sustained inflammation compromises the core neuroprote...Chronic inflammation has increasingly been acknowledged as a hallmark feature of several progressive neurodegenerative disorders. Accruing evidence indicates that sustained inflammation compromises the core neuroprotective mechanisms underlying neural injury in Alzheimer's disease (AD) and retinal neurodegenerative disorders.展开更多
Extracellular deposits of the amyloid-beta peptide(Aβ) are known as the main pathological hallmark of Alzheimer's disease. In Alzheimer's disease, neurons are injured and die throughout the brain, a process i...Extracellular deposits of the amyloid-beta peptide(Aβ) are known as the main pathological hallmark of Alzheimer's disease. In Alzheimer's disease, neurons are injured and die throughout the brain, a process in which Aβ neurotoxicity is considered to play an important role. However, the molecular mechanisms underlying Aβ toxicity that lead to neurodegeneration are not clearly established. Here we have elucidated the molecular pathways and networks which are impacted by Aβ in neurons using SH-SY5Y human neuroblastoma cells as a model. These cells were treated with Aβ_(1–42) peptides to study changes in biochemical networks using tandem mass tag labeled quantitative proteomic technique followed by computational analysis of the data. The molecular impacts of Aβ on cells were evident in a time-and dose-dependent manner, albeit the duration of treatment induced greater differential changes in cellular proteome compared to the effects of concentration. Aβ induced early changes in proteins associated with lysosomes, collagen chain trimerization and extracellular matrix receptor interaction, complement and coagulation cascade, oxidative stress induced senescence, ribosome biogenesis, regulation of insulin-like growth factor transport and uptake by insulin-like growth factor-binding protein. These novel findings provide molecular insights on the effects of Aβ on neurons, with implications for better understanding the impacts of Aβ on early neurodegeneration in Alzheimer's disease pathology.展开更多
基金supported by Ophthalmic Research Institute of Australia(ORIA),NHMRC,Macquarie University,and the Australian Government’s National Collaborative Research Infrastructure Scheme(NCRIS)
文摘Chronic inflammation has increasingly been acknowledged as a hallmark feature of several progressive neurodegenerative disorders. Accruing evidence indicates that sustained inflammation compromises the core neuroprotective mechanisms underlying neural injury in Alzheimer's disease (AD) and retinal neurodegenerative disorders.
文摘Extracellular deposits of the amyloid-beta peptide(Aβ) are known as the main pathological hallmark of Alzheimer's disease. In Alzheimer's disease, neurons are injured and die throughout the brain, a process in which Aβ neurotoxicity is considered to play an important role. However, the molecular mechanisms underlying Aβ toxicity that lead to neurodegeneration are not clearly established. Here we have elucidated the molecular pathways and networks which are impacted by Aβ in neurons using SH-SY5Y human neuroblastoma cells as a model. These cells were treated with Aβ_(1–42) peptides to study changes in biochemical networks using tandem mass tag labeled quantitative proteomic technique followed by computational analysis of the data. The molecular impacts of Aβ on cells were evident in a time-and dose-dependent manner, albeit the duration of treatment induced greater differential changes in cellular proteome compared to the effects of concentration. Aβ induced early changes in proteins associated with lysosomes, collagen chain trimerization and extracellular matrix receptor interaction, complement and coagulation cascade, oxidative stress induced senescence, ribosome biogenesis, regulation of insulin-like growth factor transport and uptake by insulin-like growth factor-binding protein. These novel findings provide molecular insights on the effects of Aβ on neurons, with implications for better understanding the impacts of Aβ on early neurodegeneration in Alzheimer's disease pathology.
