Netrin-1 protects the SH-SY5Y cells against amyloid beta neurotoxicity through NF-κB/Nrf2 dependent mechanism.

Many evidence confirms that amyloid beta 1-42 fragment (Aβ1-42) causes neuroinflammation, oxidative stress, and cell death, which are related to progressive memory loss, cognitive impairments and mental disorders that will lead to Alzheimer's disease (AD) progression. Netrin-1, as a member of the laminins, has been proved to inhibit apoptosis and inflammation outside of nervous system, in addition to having a vital role in morphogenesis and neurogenesis of neural system. This study was designed to assess the protective effects of netrin-1 in SH-SY5Y human neuroblastoma cell line exposed to Aβ1-42 and to explore some mechanisms that underlie netrin-1 effects. Cultured SH-SY5Y neuroblast-like cells were treated with netrin-1 prior to Aβ1-42 exposure and the effects were assessed by MTT and ELISA assay kits. Netrin- 1 pretreatment of Aβ1-42-exposed SH-SY5Y human neuroblastoma cells attenuated Aβ1-42 induced toxic effects, increased cell viability and partially restored levels of 3 inflammatory and oxidative stress biomarkers including: nuclear factor erythroid 2-like 2 (Nrf2), tumor necrosis factor alpha (TNFα) and nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB). Based on the findings of this study, netrin-1 represents a promising therapeutic bio agent to abrogate cellular inflammation and reactive oxygen species (ROS) activation induced by Aβ1-42 in the SH-SY5Y cell model of AD.