title: Formononetin attenuates Aβ25-35-induced cytotoxicity in HT22 cells via PI3K/Akt signaling and non-amyloidogenic cleavage of APP.
abstract: Amyloid beta (Aβ) is the main component of the amyloid plaques that accumulate in the brains of Alzheimer patients. Here, we reported the protective role of Formononetin (Form) against Aβ25-35-induced neurotoxicity in HT22 cells. We found that Form significantly increased the viability of HT22 cells but decreased the cell apoptosis when challenging with Aβ25-35.The inhibitory effects of Form were associated with PI3K/Akt signaling pathway as PI3K inhibitor (LY294002) or ERα specific inhibitor (MPP) blocked the effects. Form also accelerated the non-amyloidogenic process of amyloid precursor protein (APP) by enhancing α-secretase activity and sAPPα release. Altogether, our findings may provide a novel therapeutic target to treat AD sufferers.
authors.affiliation: Department of Anatomy, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Lizhi
authors.initials: L
authors.lastname: Chen
authors.affiliation: Department of Anatomy, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Shanshan
authors.initials: S
authors.lastname: Ou
authors.affiliation: Department of Anatomy, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Lingqi
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Anatomy, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, China.
authors.forename: Hai
authors.initials: H
authors.lastname: Tang
authors.affiliation: Department of Anatomy, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, China. Electronic address: xujie@mail.sysu.edu.cn.
authors.forename: Jie
authors.initials: J
authors.lastname: Xu
authors.affiliation: Department of Anatomy, Zhongshan Medical College, Sun Yat-Sen University, Guangzhou, China. Electronic address: guokh@mail.sysu.edu.cn.
authors.forename: Kaihua
authors.initials: K
authors.lastname: Guo
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002460:Cell Line; D007529:Isoflavones / Q000494:pharmacology*; D051379:Mice; D051058:Oncogene Protein v-akt / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D016229:Amyloid beta-Peptides; D016564:Amyloid beta-Protein Precursor; D007529:Isoflavones; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); C007768:formononetin; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt
keywords: APP; Alzheimer’s disease; ERα; Formononetin; PI3K/Akt; β-amyloid