title: Suppressive effects of SuHeXiang Wan on amyloid-β42-induced extracellular signal-regulated kinase hyperactivation and glial cell proliferation in a transgenic Drosophila model of Alzheimer's disease.
abstract: SuHeXiang Wan (SHXW), a Chinese traditional medicine, has been used to treat infantile convulsions, seizures and strokes. Previously, we reported that modified SHXW, called KSOP1009, suppressed the hyper-activation of c-Jun N-terminal kinase (JNK) and Alzheimer's disease (AD)-like phenotypes in amyloid-β42 (Aβ42)-expressing Drosophila AD models. In the present study, we, further, investigated the detailed mechanism by which KSOP1009 suppresses the AD-like phenotypes of the model flies. As seen in the brains of AD patients, pan-neuronal expression of Aβ42 in Drosophila increased activation of extracellular signal-regulated kinase (ERK), which was monitored by its phosphorylation level, and the number of glial cells in the brain. Suppression of caspase activity did not affect these phenomena, suggesting that Aβ42 induces ERK activation and glial cell proliferation independently of apoptotic processes. KSOP1009 intake significantly reduced the level of ERK activation and the number of glial cells. Moreover, KSOP1009 intake also effectively decreased the defects in the wing vein formation induced by Epidermal growth factor receptor (Egfr) overexpression in fly wings, suggesting that it may contain an inhibitory substance that inhibits the EGFR/ERK signaling pathway. In addition, the Aβ42-induced locomotive defect was partially rescued by inhibition of the elevated ERK activity through its antagonistic drug treatment. Taken together, these results suggest that KSOP1009 exerts its therapeutic effect by inhibiting the EGFR/ERK pathway and glial cell proliferation and by suppressing the JNK pathway and apoptosis.
authors.affiliation: Department of Biological Sciences, Konkuk University.
authors.forename: Seung Hwan
authors.initials: SH
authors.lastname: Park
authors.forename: Soojin
authors.initials: S
authors.lastname: Lee
authors.forename: Yoon Ki
authors.initials: YK
authors.lastname: Hong
authors.forename: Soojin
authors.initials: S
authors.lastname: Hwang
authors.forename: Jang Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Se Min
authors.initials: SM
authors.lastname: Bang
authors.forename: Young-Kyoon
authors.initials: YK
authors.lastname: Kim
authors.forename: Byung-Soo
authors.initials: BS
authors.lastname: Koo
authors.forename: Im-Soon
authors.initials: IS
authors.lastname: Lee
authors.forename: Kyoung Sang
authors.initials: KS
authors.lastname: Cho
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D030801:Animals, Genetically Modified; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004330:Drosophila; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D066246:ErbB Receptors / Q000502:physiology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006801:Humans; D009457:Neuroglia / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010766:Phosphorylation
chemical_list: D016229:Amyloid beta-Peptides; D004365:Drugs, Chinese Herbal; D018696:Neuroprotective Agents; C560536:SuHeXiang Wan; D066246:ErbB Receptors; D048049:Extracellular Signal-Regulated MAP Kinases