Alzheimer’s disease is the most frequent form of dementia characterized by the deposition of amyloid-beta plaques and neurofibrillary tangles consisting of hyperphosphorylated tau.Targeting amyloid-beta plaques has b...Alzheimer’s disease is the most frequent form of dementia characterized by the deposition of amyloid-beta plaques and neurofibrillary tangles consisting of hyperphosphorylated tau.Targeting amyloid-beta plaques has been a primary direction for developing Alzheimer’s disease treatments in the last decades.However,existing drugs targeting amyloid-beta plaques have not fully yielded the expected results in the clinic,necessitating the exploration of alternative therapeutic strategies.Increasing evidence unravels that astrocyte morphology and function alter in the brain of Alzheimer’s disease patients,with dysregulated astrocytic purinergic receptors,particularly the P2Y1 receptor,all of which constitute the pathophysiology of Alzheimer’s disease.These receptors are not only crucial for maintaining normal astrocyte function but are also highly implicated in neuroinflammation in Alzheimer’s disease.This review delves into recent insights into the association between P2Y1 receptor and Alzheimer’s disease to underscore the potential neuroprotective role of P2Y1 receptor in Alzheimer’s disease by mitigating neuroinflammation,thus offering promising avenues for developing drugs for Alzheimer’s disease and potentially contributing to the development of more effective treatments.展开更多
Stem-leaf saponins from Panax notoginseng(SLSP)comprise numerous PPD-type saponins with diverse pharmacological properties;however,their role in Parkinson's disease(PD),characterized by microglia-mediated neuroinf...Stem-leaf saponins from Panax notoginseng(SLSP)comprise numerous PPD-type saponins with diverse pharmacological properties;however,their role in Parkinson's disease(PD),characterized by microglia-mediated neuroinflammation,remains unclear.This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models,including the 1-methyl-4-phenylpyridinium(MPTP)-induced mouse model and lipopolysaccharide(LPS)-stimulated BV-2 microglia.Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD,including MPTP-treated mice.Additionally,SLSP inhibited the upregulation of inducible nitric oxide synthase(i NOS)and cyclooxygenase-2(COX2)and attenuated the phosphorylation of PI3K,protein kinase B(AKT),nuclear factor-κB(NFκB),and inhibitor of NFκB proteinα(IκBα)both in vivo and in vitro.Moreover,SLSP suppressed the production of inflammatory markers such as interleukin(IL)-1β,IL-6,and tumor necrosis factor alpha(TNF-α)in LPS-stimulated BV-2cells.Notably,the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPStreated BV-2 cells.These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models,likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway.These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.展开更多
文摘Alzheimer’s disease is the most frequent form of dementia characterized by the deposition of amyloid-beta plaques and neurofibrillary tangles consisting of hyperphosphorylated tau.Targeting amyloid-beta plaques has been a primary direction for developing Alzheimer’s disease treatments in the last decades.However,existing drugs targeting amyloid-beta plaques have not fully yielded the expected results in the clinic,necessitating the exploration of alternative therapeutic strategies.Increasing evidence unravels that astrocyte morphology and function alter in the brain of Alzheimer’s disease patients,with dysregulated astrocytic purinergic receptors,particularly the P2Y1 receptor,all of which constitute the pathophysiology of Alzheimer’s disease.These receptors are not only crucial for maintaining normal astrocyte function but are also highly implicated in neuroinflammation in Alzheimer’s disease.This review delves into recent insights into the association between P2Y1 receptor and Alzheimer’s disease to underscore the potential neuroprotective role of P2Y1 receptor in Alzheimer’s disease by mitigating neuroinflammation,thus offering promising avenues for developing drugs for Alzheimer’s disease and potentially contributing to the development of more effective treatments.
基金supported by the Educational Commission of Shanghai in China(No.2021LK114)the Organizational Key Research and Development Program of Shanghai University of Traditional Chinese Medicine(No.2023YZZ02)the Xinglin Young Talent Program at Shanghai University of Traditional Chinese Medicine(No.A1-U17205010430)。
文摘Stem-leaf saponins from Panax notoginseng(SLSP)comprise numerous PPD-type saponins with diverse pharmacological properties;however,their role in Parkinson's disease(PD),characterized by microglia-mediated neuroinflammation,remains unclear.This study evaluated the effects of SLSP on suppressing microglia-driven neuroinflammation in experimental PD models,including the 1-methyl-4-phenylpyridinium(MPTP)-induced mouse model and lipopolysaccharide(LPS)-stimulated BV-2 microglia.Our findings revealed that SLSP mitigated behavioral impairments and excessive microglial activation in models of PD,including MPTP-treated mice.Additionally,SLSP inhibited the upregulation of inducible nitric oxide synthase(i NOS)and cyclooxygenase-2(COX2)and attenuated the phosphorylation of PI3K,protein kinase B(AKT),nuclear factor-κB(NFκB),and inhibitor of NFκB proteinα(IκBα)both in vivo and in vitro.Moreover,SLSP suppressed the production of inflammatory markers such as interleukin(IL)-1β,IL-6,and tumor necrosis factor alpha(TNF-α)in LPS-stimulated BV-2cells.Notably,the P2Y2R agonist partially reversed the inhibitory effects of SLSP in LPStreated BV-2 cells.These results suggest that SLSP inhibit microglia-mediated neuroinflammation in experimental PD models,likely through the P2Y2R/PI3K/AKT/NFκB signaling pathway.These novel findings indicate that SLSP may offer therapeutic potential for PD by attenuating microglia-mediated neuroinflammation.
