Alzheimer's disease(AD)is the most prevalent neurodegenerative disorder affecting the elderly.Among its pathological mechanisms,neuroinflammation triggered by amyloid-β(Aβ)aggregation is considered a key contrib...Alzheimer's disease(AD)is the most prevalent neurodegenerative disorder affecting the elderly.Among its pathological mechanisms,neuroinflammation triggered by amyloid-β(Aβ)aggregation is considered a key contributor.Alternatively activated(M2)macrophages and microglia have been shown to play a pivotal role in curbing neuroinflammation,thereby offering neuroprotective effects in neurodegenerative diseases.In the present study,we explored the therapeutic potential ofα-galactosylceramide(α-Galcer)in enhancing learning and memory functions in AD model mice while delving into its underlying mechanisms.Our findings demonstrated thatα-Galcer administration lowered the interferon regulatory factor(IRF)5/IRF4 ratio,leading to a higher proportion of M2 microglia and macrophages.These beneficial effects were achieved by modulating the expression of inflammation-related cytokines in the brains of AD model mice,thereby accelerating the resolution of neuroinflammation and ultimately enhancing cognitive performance.展开更多
In the present study,we aimed to evaluate the anti-inflammatory mechanism of galanthamine,a classic therapeutic drug for Alzheimer s disease(AD).The co-culture system of hippocampal nerve cell line HT-22 and microglia...In the present study,we aimed to evaluate the anti-inflammatory mechanism of galanthamine,a classic therapeutic drug for Alzheimer s disease(AD).The co-culture system of hippocampal nerve cell line HT-22 and microglial cell line BV-2 was established to observe the effect of galanthamine on the expressions of inflammatory factors induced by lipopolysaccharide(LP S).MTT method was used to observe the protective effect of galanthamine on neurons.ELISA and qPCR methods were used to detect the expressions of interleukin-β(IL-1β) and IL-1 receptor antagonist(IL-1 RA) at the protein and mRNA levels,respectively.IL-1β and IL-1 RA were evaluated by the ELISA method after pretreating with galanthamine and α7 nAChR blockerα-bungarotoxin(α-bun),mAChR blocker atropine(Atr),PI3 K inhibitor LY294002,IKKβ inhibitor SC514,or MEK inhibitor PD98059,respectively.The results showed that galanthamine significantly inhibited LPS-induced increased IL-1β and IL-1 RA expressions and maintained the ratio of IL-1β/IL-1 RA.α-Bun could block the regulatory effect of galanthamine on IL-1β and IL-1 RA.As PI3 K and NF-κB pathways were blocked,the regulatory effect of galanthamine on the IL-1β expression was significantly inhibited.Blocking PI3 K and MEK pathways could significantly inhibit the regulation of galanthamine on IL-1 RA expression.In summary,galanthamine regulated the inflammatory activity of the IL-1 subfamily to play an anti-inflammatory role mediated by α7 nAChR and PI3 K/NF-κB/MAPK pathways,which probably provided a new strategy for AD treatment.展开更多
基金National Natural Science Foundation of China(Grant No.81100801)。
文摘Alzheimer's disease(AD)is the most prevalent neurodegenerative disorder affecting the elderly.Among its pathological mechanisms,neuroinflammation triggered by amyloid-β(Aβ)aggregation is considered a key contributor.Alternatively activated(M2)macrophages and microglia have been shown to play a pivotal role in curbing neuroinflammation,thereby offering neuroprotective effects in neurodegenerative diseases.In the present study,we explored the therapeutic potential ofα-galactosylceramide(α-Galcer)in enhancing learning and memory functions in AD model mice while delving into its underlying mechanisms.Our findings demonstrated thatα-Galcer administration lowered the interferon regulatory factor(IRF)5/IRF4 ratio,leading to a higher proportion of M2 microglia and macrophages.These beneficial effects were achieved by modulating the expression of inflammation-related cytokines in the brains of AD model mice,thereby accelerating the resolution of neuroinflammation and ultimately enhancing cognitive performance.
基金National Natural Science Foundation of China (Grant No. 81100801)Peking Union Medical College Small-Scale Characteristic School Education Project。
文摘In the present study,we aimed to evaluate the anti-inflammatory mechanism of galanthamine,a classic therapeutic drug for Alzheimer s disease(AD).The co-culture system of hippocampal nerve cell line HT-22 and microglial cell line BV-2 was established to observe the effect of galanthamine on the expressions of inflammatory factors induced by lipopolysaccharide(LP S).MTT method was used to observe the protective effect of galanthamine on neurons.ELISA and qPCR methods were used to detect the expressions of interleukin-β(IL-1β) and IL-1 receptor antagonist(IL-1 RA) at the protein and mRNA levels,respectively.IL-1β and IL-1 RA were evaluated by the ELISA method after pretreating with galanthamine and α7 nAChR blockerα-bungarotoxin(α-bun),mAChR blocker atropine(Atr),PI3 K inhibitor LY294002,IKKβ inhibitor SC514,or MEK inhibitor PD98059,respectively.The results showed that galanthamine significantly inhibited LPS-induced increased IL-1β and IL-1 RA expressions and maintained the ratio of IL-1β/IL-1 RA.α-Bun could block the regulatory effect of galanthamine on IL-1β and IL-1 RA.As PI3 K and NF-κB pathways were blocked,the regulatory effect of galanthamine on the IL-1β expression was significantly inhibited.Blocking PI3 K and MEK pathways could significantly inhibit the regulation of galanthamine on IL-1 RA expression.In summary,galanthamine regulated the inflammatory activity of the IL-1 subfamily to play an anti-inflammatory role mediated by α7 nAChR and PI3 K/NF-κB/MAPK pathways,which probably provided a new strategy for AD treatment.
