Roles of receptor-interacting protein kinase 1 in SH-SY5Y cells with beta amyloid-induced neurotoxicity

Alzheimer's disease (AD), the major cause of dementia, affects the elderly population worldwide. Previous studies have shown that depletion of receptor-interacting protein kinase 1 (RIPK1) expression reverted the AD phenotype in murine AD models. Necroptosis, executed by mixed lineage kinase domain-like (MLKL) protein and activated by RIPK1 and RIPK3, has been shown to be involved in AD. However, the role of RIPK1 in beta-amyloid (A beta)-induced necroptosis is not yet fully understood. In this study, we explored the role of RIPK1 in the SH-SY5Y human neuroblastoma cells treated with A beta 1-40 or A beta 1-42. We showed that A beta-induced neuronal cell death was independent of apoptosis and autophagy pathways. Further analyses depicted that activation of RIPK1/MLKL-dependant necroptosis pathway was observed in vitro. We demonstrated that inhibition of RIPK1 expression rescued the cells from A beta-induced neuronal cell death and ectopic expression of RIPK1 was found to enhance the stability of the endogenous APP. In summary, our findings demonstrated that A beta can potentially drive necroptosis in an RIPK1-MLKL-dependent manner, proposing that RIPK1 plays an important role in the pathogenesis of AD.

Automated summary

This study explored the role of RIPK1 in A beta-induced necroptosis. It was found that A beta can activate the RIPK1-MLKL-dependent necroptosis pathway, leading to neuronal cell death. Inhibition of RIPK1 expression rescued cells from A beta-induced cell death, while ectopic expression of RIPK1 enhanced the stability of endogenous APP.