title: PEG-PEI/siROCK2 Protects Against Aβ42-Induced Neurotoxicity in Primary Neuron Cells for Alzheimer Disease.
abstract: Gene therapy that targets the ROCK2 gene has yielded promising results in the treatment of AD. Our previous study indicated that PEG-PEI/siROCK2 could effectively suppress ROCK2 mRNA expression and showed a promising prospect for the treatment of Alzheimer's disease. However, the ability of PEG-PEI/siROCK2 to reduce Aβ-induced cytotoxicity is unknown. To investigate the effect of PEG-PEI/siROCK2 against Aβ42-induced neurotoxicity, primary cultured cortical neurons were pretreated with PEG-PEI/siROCK2 for 24 h and then treated with 5 μM Aβ42 for 24 h. We found that PEG-PEI/siROCK2 increased the cell viability and reduced the number of apoptotic cells induced by Aβ42, as measured using an MTT assay and Annexin V/PI staining. A further study revealed that PEG-PEI/siROCK2 can activate p-Akt, and treatment with the PI3K inhibitor LY294002 attenuated the neuroprotective effects. These results suggest that PEG-PEI/siROCK2 prevents Aβ42-induced neurotoxicity and that the activation of PI3K/Akt pathway is involved in neuroprotection. Taken together, these findings shed light on the role of PEG-PEI/siROCK2 as a potential therapeutic agent for AD.
authors.affiliation: Department of Neurology, The Sixth Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China.
authors.forename: Yunyun
authors.initials: Y
authors.lastname: Liu
authors.forename: Xingyi
authors.initials: X
authors.lastname: Yang
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: Lei
authors.forename: Zhong
authors.initials: Z
authors.lastname: Li
authors.forename: Jingyang
authors.initials: J
authors.lastname: Hu
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Wen
authors.forename: Huijun
authors.initials: H
authors.lastname: Wang
authors.forename: Zhonglin
authors.initials: Z
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000628:therapy*; D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004337:Drug Carriers / Q000737:chemistry; D004622:Embryo, Mammalian; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D051379:Mice; D058990:Molecular Targeted Therapy / Q000379:methods; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage* / Q000494:pharmacology; D010446:Peptide Fragments / Q000633:toxicity*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011094:Polyethyleneimine / Q000031:analogs & derivatives* / Q000737:chemistry; D061251:Primary Cell Culture; D034741:RNA, Small Interfering / Q000008:administration & dosage* / Q000494:pharmacology; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000235:genetics
chemical_list: D016229:Amyloid beta-Peptides; D004337:Drug Carriers; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D034741:RNA, Small Interfering; C075222:amyloid beta-protein (1-42); C544016:poly(ethylene glycol)-co-poly(ethyleneimine); D011092:Polyethylene Glycols; D011094:Polyethyleneimine; C515855:Rock2 protein, mouse; D054460:rho-Associated Kinases