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
AIM To evaluate the role of P2Y1 R in visceral hypersensitivity in rats with experimental irritable bowel syndrome.METHODS A rat model of irritable bowel syndrome was generated by intra-colonic administration of aceti...AIM To evaluate the role of P2Y1 R in visceral hypersensitivity in rats with experimental irritable bowel syndrome.METHODS A rat model of irritable bowel syndrome was generated by intra-colonic administration of acetic acid(AA) and assessed by histology and myeloperoxidase(m PO) activity assay. Then P2Y1 R expression in the colonic tissue was detected by Western blot. In order to explore the regulatory role of P2Y1 R in visceral hypersensitivity, an agonist(m RS2365) and an antagonist(m RS2179) of P2Y1 R were intra-colonically administered and effects were tested through a colorectal distension test. The abdominal withdrawal reflex and abdominal electromyography were tested during the course. RESULTS model assessment tests showed an obvious inflammatoryreaction that appeared on the 2^(nd) d after the AA injection, and the inflammatory reaction gradually recovered and almost disappeared on the 7^(th) d. The model finished on day 8 and showed a clear feature of IBS that had no organic lesion. The average expression of P2Y1 R was significantly higher in the AA group than in the na?ve group(0.319 ± 0.02 vs 0.094 ± 0.016, P < 0.001). m RS2365 could effectively raise the colonic hypersensitivity status at intervention doses of 10(AUC value from 0.30 ± 0.089 to 1.973 ± 0.127 mv?s, P < 0.01) and 100 μmol/L(AUC value from 0.290 ± 0.079 to 1.983 ± 0.195 mv?s, P < 0.01); m RS2179 could effectively reduce the hypersensitivity status at intervention dose of 100 μmol/L(from a mean baseline AUC value of 1.587 ± 0.099 mv?s to 0.140 ± 0.089 mv?s, P < 0.0001). Differences between the m RS2179 group(1.88 ± 1.45) and either the m RS2365 group(3.96 ± 0.19) or the combined treatment(m RS2179 and m RS2365) group(3.28 ± 0.11) were significant(P < 0.01).CONCLUSION P2Y1 R plays a regulatory role in visceral hypersensitivity in rats with experimental IBS. Specific antagonists of P2Y1 R may have potential therapeutic value in treating abdominal pain in IBS.展开更多
Platelets aggregation and thrombosis formation are major reasons of cardiovascular and cerebral vascular diseases.To develop novel,effective and safe agents for inhibiting platelet aggregation and preventing above dis...Platelets aggregation and thrombosis formation are major reasons of cardiovascular and cerebral vascular diseases.To develop novel,effective and safe agents for inhibiting platelet aggregation and preventing above diseases is urgently needed.Some traditional Chinese medicines for“Houxue Huayu”have been shown to inhibit platelet aggregation potently.They are used frequently in China and also in Asian countries.Recently,the major effective components of Pueraria lobata,Salvia miltiorrhiza Bunge,Apium graveolens L.and so on were studied.The mechanisms and the molecular targets of puerarin,salvianolic acid B and the analogue of 3-n-butylphthalide,dl-PHPB were investigated.Four platelet aggregation inducers,ADP,arachidonic acid(AA),collagen(Col)and thrombin,were used in the study.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 MIMS(Shanghai)Ltd.of China,No.IDF-2013-07
文摘AIM To evaluate the role of P2Y1 R in visceral hypersensitivity in rats with experimental irritable bowel syndrome.METHODS A rat model of irritable bowel syndrome was generated by intra-colonic administration of acetic acid(AA) and assessed by histology and myeloperoxidase(m PO) activity assay. Then P2Y1 R expression in the colonic tissue was detected by Western blot. In order to explore the regulatory role of P2Y1 R in visceral hypersensitivity, an agonist(m RS2365) and an antagonist(m RS2179) of P2Y1 R were intra-colonically administered and effects were tested through a colorectal distension test. The abdominal withdrawal reflex and abdominal electromyography were tested during the course. RESULTS model assessment tests showed an obvious inflammatoryreaction that appeared on the 2^(nd) d after the AA injection, and the inflammatory reaction gradually recovered and almost disappeared on the 7^(th) d. The model finished on day 8 and showed a clear feature of IBS that had no organic lesion. The average expression of P2Y1 R was significantly higher in the AA group than in the na?ve group(0.319 ± 0.02 vs 0.094 ± 0.016, P < 0.001). m RS2365 could effectively raise the colonic hypersensitivity status at intervention doses of 10(AUC value from 0.30 ± 0.089 to 1.973 ± 0.127 mv?s, P < 0.01) and 100 μmol/L(AUC value from 0.290 ± 0.079 to 1.983 ± 0.195 mv?s, P < 0.01); m RS2179 could effectively reduce the hypersensitivity status at intervention dose of 100 μmol/L(from a mean baseline AUC value of 1.587 ± 0.099 mv?s to 0.140 ± 0.089 mv?s, P < 0.0001). Differences between the m RS2179 group(1.88 ± 1.45) and either the m RS2365 group(3.96 ± 0.19) or the combined treatment(m RS2179 and m RS2365) group(3.28 ± 0.11) were significant(P < 0.01).CONCLUSION P2Y1 R plays a regulatory role in visceral hypersensitivity in rats with experimental IBS. Specific antagonists of P2Y1 R may have potential therapeutic value in treating abdominal pain in IBS.
文摘Platelets aggregation and thrombosis formation are major reasons of cardiovascular and cerebral vascular diseases.To develop novel,effective and safe agents for inhibiting platelet aggregation and preventing above diseases is urgently needed.Some traditional Chinese medicines for“Houxue Huayu”have been shown to inhibit platelet aggregation potently.They are used frequently in China and also in Asian countries.Recently,the major effective components of Pueraria lobata,Salvia miltiorrhiza Bunge,Apium graveolens L.and so on were studied.The mechanisms and the molecular targets of puerarin,salvianolic acid B and the analogue of 3-n-butylphthalide,dl-PHPB were investigated.Four platelet aggregation inducers,ADP,arachidonic acid(AA),collagen(Col)and thrombin,were used in the study.
