PEG–PEI/siROCK2 Protects Against Aβ 42 -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.