title: EGb761 protects against Aβ1-42 oligomer-induced cell damage via endoplasmic reticulum stress activation and Hsp70 protein expression increase in SH-SY5Y cells.
abstract: Studies have shown that misfolded proteins and endoplasmic reticulum (ER) stress play pivotal roles in the progression of Alzheimer's disease (AD). It has also been reported that ER stress is considered to be a common mediator of apoptosis in neurodegenerative disorders like AD. However, the precise mechanisms leading to neuronal cell death caused by ER stress in AD remain unclear. Hsp70, the major inducible form of the heat shock protein family, functions at the level of chaperone-mediated protein folding. Enhanced expression of Hsp70 suppresses the neurotoxicity caused by protein misfolding. EGb761, an accepted traditional Chinese medicine used to treat AD, was used here to examine the molecular mechanism underlying its protective effect on ER stress and Hsp70. Our study shows that pretreatment with EGb761 overcomes the neurotoxicity of the Aβ1-42 oligomer by increasing Hsp70, Grp78, IRE1α and pAkt expression in a dose-dependent manner and significantly decreases cell apoptosis-related protein expression. Our findings suggest that the neuroprotective effect of EGb761 is related to ER stress activation and increased Hsp70 expression, and subsequent activation of Akt. However, the effect of EGb761 on these processes is not direct.
authors.affiliation: Department of integrated Chinese and Western Medicine, Huashan Hospital, Fudan University, Shanghai, PR China; Geriatrics Department of Chinese Medicine, Huadong Hospital, Fusan University, Shanghai, PR China.
authors.forename: Lumei
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Chinese Medicine, Dongfang Hospital, Tongji University, Shanghai, PR China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Zhang
authors.affiliation: Department of Perinatal Medicine Pregnancy Research Centre and University of Melbourne Department of Obstetrics and Gynaecology, Royal Women's Hospital, Parkville 3052, Australia.
authors.forename: Bill
authors.initials: B
authors.lastname: Kalionis
authors.affiliation: Department of Neurology, Zhongshan Hospital, Fudan University, Shanghai, PR China.
authors.forename: Wenbin
authors.initials: W
authors.lastname: Wan
authors.affiliation: Department of Obstetrics & Gynaecology, University of Melbourne, Parkville, VIC, Australia.
authors.forename: Padma
authors.initials: P
authors.lastname: Murthi
authors.affiliation: Shanghai Geriatric Institute of Chinese Medicine, Shanghai, PR China.
authors.forename: Chuan
authors.initials: C
authors.lastname: Chen
authors.affiliation: Geriatrics Department of Chinese Medicine, Huadong Hospital, Fusan University, Shanghai, PR China. Electronic address: doctorymli@163.com.
authors.forename: Yaming
authors.initials: Y
authors.lastname: Li
authors.affiliation: Shanghai Key Laboratory of Clinical Geriatrics, Shanghai Institute of Geriatrics, Huadong Hospital, Fudan University, Shanghai, PR China. Electronic address: xiashijinhd@163.com.
authors.forename: Shijin
authors.initials: S
authors.lastname: Xia
mesh_terms: D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D000091342:Endoplasmic Reticulum Chaperone BiP; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects* / Q000502:physiology; D020441:Ginkgo biloba; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis*; D006801:Humans; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D010936:Plant Extracts / Q000008:administration & dosage / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation / Q000187:drug effects; D000096983:Ginkgo Extract
chemical_list: D016229:Amyloid beta-Peptides; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D010936:Plant Extracts; D051057:Proto-Oncogene Proteins c-akt; C000717247:HSPA5 protein, human; C075222:amyloid beta-protein (1-42); C063170:Ginkgo biloba extract; D000096983:Ginkgo Extract
keywords: Akt; Alzheimer's disease; EGb761; Endoplasmic reticulum stress; Hsp70