机构：[1]Hebei Med Univ, Dept Clin Pharmacol, Hosp 4, Shijiazhuang, Hebei, Peoples R China药学部药学部河北医科大学第四医院[2]Hebei Med Univ, Breast Ctr, Hosp 4, 12 Jiankang Rd, Shijiazhuang, Hebei, Peoples R China临床科室外一科河北医科大学第四医院[3]Quanzhou Normal Univ, Phys Educ Dept, Quanzhou, Fujian, Peoples R China[4]Bethune Int Peace Hosp, Dept Pharm, Shijiazhuang, Hebei, Peoples R China
Neuroinflammation and autophagy dysfunction are known to be involved in the pathological procession of Alzheimer's disease (AD). Progesterone (PG), neuroactive steroids, exerts a characteristic neuroprotective function in improving AD syndrome. The NOD-like receptor pyrin 3 (NLRP3)-Caspase-1 inflammasome has specific relevance to AD pathological procession. However, the exact role of PG in regulating NLRP3-Caspase-1 inflammasome remains to be elucidated. We demonstrated A beta up-regulated IL-1 beta expression in astrocytes by activating NLRP3-Caspase-1 inflammasome. However, pharmacological activation of autophagy by Rapamycin (RAPA) efficiently suppressed A beta-, lipopolysaccharides (LPS)-induced IL-1 beta expression via regulating NLRP3-Caspase-1 inflammasome in astrocytes. Remarkably, PG significantly inhibited A beta-induced NLRP3-Caspase-1 inflammasome activation. Autophagy inhibitor 3-MA blocked the protective effects of PG in mediating NLRP3 inflammasome and IL-1 beta processing. Taken together, our observations suggest that autophagy-lysosome pathway is one specific molecular mechanism in regulating A beta-induced NLRP3-Caspase-1 inflammasome activation in astrocytes, particularly uncover the potential neuroprotection of PG in regulating upstream signaling leading to the sequence events of neuroinflammation. That neuroprotective mechanism of PG in regulating NLRP3-Caspase-1 inflammasome can be a potential therapeutic target for ameliorating the pathological procession of AD.
第一作者机构：[1]Hebei Med Univ, Dept Clin Pharmacol, Hosp 4, Shijiazhuang, Hebei, Peoples R China
通讯作者：
通讯机构：[2]Hebei Med Univ, Breast Ctr, Hosp 4, 12 Jiankang Rd, Shijiazhuang, Hebei, Peoples R China[*1]Breast Center, The Fourth Hospital of Hebei Medical University, No.12 Jiankang Road, Shijiazhuang, Hebei Province, China.
推荐引用方式(GB/T 7714)：
Hong Yang,Liu Yunjiang,Yu Dongzhen,et al.The neuroprotection of progesterone against A beta-induced NLRP3-Caspase-1 inflammasome activation via enhancing autophagy in astrocytes[J].INTERNATIONAL IMMUNOPHARMACOLOGY.2019,74:doi:10.1016/j.intimp.2019.05.054.
APA：
Hong, Yang,Liu, Yunjiang,Yu, Dongzhen,Wang, Mingxia&Hou, Yanning.(2019).The neuroprotection of progesterone against A beta-induced NLRP3-Caspase-1 inflammasome activation via enhancing autophagy in astrocytes.INTERNATIONAL IMMUNOPHARMACOLOGY,74,
MLA：
Hong, Yang,et al."The neuroprotection of progesterone against A beta-induced NLRP3-Caspase-1 inflammasome activation via enhancing autophagy in astrocytes".INTERNATIONAL IMMUNOPHARMACOLOGY 74.(2019)
