title: Puerarin suppression of Aβ1-42-induced primary cortical neuron death is largely dependent on ERβ.
abstract: Recent study has suggested that estrogen replacement therapy (ERT) can decrease the risk of the development of Alzheimer's disease (AD), and phytoestrogen has been proposed as a potential alternative to ERT. In this study, we investigated the protective function of puerarin (a phytoestrogen isolated from puerarin lobate) against amyloid beta (Aβ1-42)-induced toxicity in cortical neurons and established the connection between such a protection and estrogen receptor (ER) activation. Puerarin suppressed Aβ1-42-induced cortical neuron death in a concentration-dependent manner. Morphological examination showed that puerarin not only suppressed Aβ1-42-induced decrease in neuron numbers, but also promoted neurite growth. In addition, we found that the neuroprotection of puerarin was dependent on the activation of estrogen receptors (ERs), as demonstrated by activation of ERE-reporter gene. Puerarin preferentially up-regulated the expression of ERβ but not ERα, and ERβ-specific siRNA significantly reduced the neuroprotection of puerarin. Taken together, our results indicated that puerarin is neuroprotective against Aβ1-42toxicity via the activation of estrogen receptors, and ERβ plays a key role in the process. Our novel findings provide a potential strategy for the prevention of neurodegeneration and the treatment of AD.
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116023, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116023, China.
authors.forename: Zuguang
authors.initials: Z
authors.lastname: Xue
authors.affiliation: Department of Radiology, The Third Hospital of Xiamen, Xiamen, Fujian 361011, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116023, China.
authors.forename: Xueyu
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Central Laboratory, Dalian Municipal Central Hospital, Dalian, Liaoning 116037, China. Electronic address: dew_whs@163.com.
authors.forename: Heshuang
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Hematology, The Second Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116023, China. Electronic address: physician_wang@126.com.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Wang
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004353:Drug Evaluation, Preclinical; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D007529:Isoflavones / Q000494:pharmacology*; D051379:Mice; D000071446:Neuronal Outgrowth / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000633:toxicity*; D034741:RNA, Small Interfering
chemical_list: D016229:Amyloid beta-Peptides; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D007529:Isoflavones; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C075222:amyloid beta-protein (1-42); C033607:puerarin
keywords: Alzheimer’s disease; Amyloid beta; Cortical neuron; Estrogen receptor; Neuroprotection; Puerarin