title: Carnosic Acid Prevents Beta-Amyloid-Induced Injury in Human Neuroblastoma SH-SY5Y Cells via the Induction of Autophagy.
abstract: Beta-amyloid (Aβ), the hallmark protein in Alzheimer's disease (AD), induces neurotoxicity that involves oxidative stress and mitochondrial dysfunction, leading to cell death. Carnosic acid (CA), a polyphenolic diterpene isolated from the herb rosemary (Rosemarinus officinalis), was investigated in our study to assess its neuroprotective effect and underlying mechanism against Aβ-induced injury in human neuroblastoma SH-SY5Y cells. We found that CA pretreatment alleviated the Aβ25-35-induced loss of cell viability, inhibited both Aβ1-42 accumulation and tau hyperphosphorylation, reduced reactive oxygen species generation, and maintained the mitochondrial membrane potential. Moreover, CA increased the microtubule-associated protein light chain 3 (LC3)-II/I ratio and decreased SQSTM1(p62), indicating that CA could induce autophagy. Autophagy inhibitor 3-methyladenine (3-MA) attenuated the neuroprotective effect of CA, suggesting that autophagy was involved in the neuroprotection of CA. It was also observed that CA activated AMP-activated protein kinase (AMPK) but inhibited mammalian target of rapamycin (mTOR). Furthermore, blocking AMPK with si-AMPKα successfully inhibited the upregulation of LC3-II/I, prevented the downregulation of phosphorylation of mTOR and SQSTM1(p62), indicating that CA induced autophagy in SH-SY5Y cells via the activation of AMPK. These results suggested that CA might be a potential agent for preventing AD.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Rd, Xi'an, 710061, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Anesthesia and Perioperative Care, Center for Cerebrovascular Research, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Hua
authors.initials: H
authors.lastname: Su
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Xi'an Jiaotong University, 277 West Yanta Rd, Xi'an, 710061, China. quqiuminxjsn@163.com.
authors.forename: Qiu-Min
authors.initials: QM
authors.lastname: Qu
mesh_terms: D045784:Abietanes / Q000494:pharmacology*; D000544:Alzheimer Disease / Q000517:prevention & control; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D006801:Humans; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D045784:Abietanes; D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D017382:Reactive Oxygen Species; C074636:amyloid beta-protein (25-35); C018381:salvin
keywords: AMP-activated protein kinase; Alzheimer’s disease; Autophagy; Carnosic acid; Neuroprotection